bluuebunny/crossref_metadata_2025 huggingface dataset:
Perirhinal cortex neuronal activity related to long‐term familiarity memory in the macaque
Authors: Hölscher Christian , Rolls Edmund T. , Xiang Jianzhong
Published: October 2003

Lesion studies suggest that the perirhinal cortex plays a role in object recognition memory. To analyse its role, the activity of single neurons in the perirhinal cortex was recorded in three rhesus monkeys (Macaca mulatta) performing a delayed matching‐to‐sample task with up to three intervening stimuli. A set of familiar visual stimuli was used. Some neurons had activity related to working memory, in that they responded more to the sample than to the match image within a trial, as shown previously. However, when a novel set of stimuli was introduced, the neuronal responses were on average only 47% of the magnitude of the responses to the familiar set of stimuli. Moreover, it was shown in eight different replications in three monkeys that the responses of the perirhinal cortex neurons gradually increased over hundreds of presentations of the new set of (initially novel) stimuli to become as large as with the already familiar stimuli. The mean number of 1.3‐s presentations to induce this effect was 400 occurring over 7–13 days. These results show that perirhinal cortex neurons represent the very long‐term familiarity of visual stimuli. A representation of the long‐term familiarity of visual stimuli may be important for many aspects of social behaviour, and part of the impairment in temporal lobe amnesia may be related to the difficulty of building representations of the degree of familiarity of stimuli.
Hypocretin‐1 causes G protein activation and increases ACh release in rat pons
Authors: Bernard René , Lydic Ralph , Baghdoyan Helen A.
Published: October 2003

The effects of the arousal‐promoting peptide hypocretin on brain stem G protein activation and ACh release were examined using 16 adult Sprague‐Dawley rats. In vitro[35S]GTPγS autoradiography was used to test the hypothesis that hypocretin‐1‐stimulated G protein activation is concentration‐dependent and blocked by the hypocretin receptor antagonist SB‐334867. Activated G proteins were quantified in dorsal raphe nucleus (DR), locus coeruleus (LC) and pontine reticular nucleus oral part (PnO) and caudal part (PnC). Concentration–response data revealed a significant (P < 0.001) effect of hypocretin‐1 (2–2000 nm) in all brain regions examined. Maximal increases over control levels of [35S]GTPγS binding were 37% (DR), 58% (LC), 52% (PnO) and 44% (PnC). SB‐334867 (2 µm) significantly (P < 0.002) blocked hypocretin‐1 (200 nm)‐stimulated [35S]GTPγS binding in all four nuclei. This is the first autoradiographic demonstration that hypocretin‐1 activates G proteins in arousal‐related brain stem nuclei as a result of specific receptor interactions. This finding suggests that some hypocretin receptors in brain stem couple to inhibitory G proteins. In vivo microdialysis was used to test the hypothesis that PnO administration of hypocretin‐1 increases ACh release in PnO. Dialysis delivery of hypocretin‐1 (100 µm) significantly (P < 0.002) increased (87%) ACh release. This finding is consistent with the interpretation that one mechanism by which hypocretin promotes arousal is by enhancing cholinergic neurotransmission in the pontine reticular formation.
Preshaping and continuous evolution of motor cortical representations during movement preparation
Authors: Bastian Annette , Schöner Gregor , Riehle Alexa
Published: October 2003

While a goal‐directed movement is prepared, motor cortical neurons selectively change their activity in relation to prior information about movement direction. Only little is known, however, about the neuronal representation of partial information about this parameter. We investigated this question by training monkeys in a multidirectional centre‐out pointing task. A preparatory signal provided prior information about one, two or three possible adjacent targets, thus manipulating the level of certainty about movement direction. After a 1‐s delay, the response signal specified one of the precued targets to indicate the actual movement to be performed. Based on the directional tuning curves of individual motor cortical neurons determined during the reaction time interval, we constructed distributions of the population activation (DPAs), which we were then able to estimate as well during the preparatory period. We found that these distributions were preshaped by prior information, with peaks of activation centred over the range of precued movement directions. These peaks sharpened as the response signal approached, and shifted to the specified movement direction subsequent to that signal. Wider ranges of precued movement directions were represented by broader DPAs. Trials in which monkeys produced short reaction times were characterized by narrower distributions than trials with long reaction times. Our study thus provides evidence for (i) a graded preshaping of the neuronal population representation of movement direction by partial information about this parameter, and (ii) the continuous evolution of the preshaped population representation during the preparatory period towards movement initiation.
Characterization of the rat A2A adenosine receptor gene: a 4.8‐kb promoter‐proximal DNA fragment confers selective expression in the central nervous system
Authors: Lee Yi‐Chao , Chien Chen‐Li , Sun Chung‐Nan , Huang Chuen‐Lin , Huang Nai‐Kuei , Chiang Ming‐Chang , Lai Hsing‐Lin , Lin Yow‐Sien , Chou Szu‐Yi , Wang Chi‐Kuang Leo , Tai Ming‐Hong , Liao Wen‐Lin , Lin Teng‐Nan , Liu Fu‐Chin , Chern Yijuang
Published: October 2003

We isolated and characterized a 4.8‐kb 5′ flanking region of the rat A2A adenosine receptor (A2A‐R) gene in the present study. Promoter activity was observed with this DNA fragment in PC12 cells and C6 cells which contain endogenous A2A‐Rs. A fusion fragment consisting of the 4.8‐kb promoter‐proximal DNA fragment of the A2A‐R gene, and the coding region of lacZ was utilized to produce mice harbouring the fusion gene. In three independent founder lines, proteins and transcripts of the transgene were found in many areas of the central nervous system (CNS), but not in three peripheral tissues examined. Double immunohistochemical analyses revealed that the transgene was coexpressed with endogenous A2A‐R and proper neuronal markers in the brain. Specifically, the transgene in the striatum was found in the enkephalin‐containing GABAergic neurons and in the cholinergic neurons as was found for the endogenous A2A‐R. However, a selectively enriched striatal expression of the transgene was not found as was observed for the endogenous A2A‐R. Collectively, the 4.8‐kb promoter‐proximal DNA fragment of the rat A2A‐R gene contains important element(s) to direct its expression in the CNS where functional A2A‐R are found, but were not sufficient to confer the highly concentrated expression of the striatal A2A‐R. Furthermore, expressions of A2A‐R and the transgene were found in both neurons and astrocytes, suggesting that adenosine might mediate its function through A2A‐R in both cell types.
Retrospective and prospective persistent activity induced by Hebbian learning in a recurrent cortical network
Authors: Mongillo Gianluigi , Amit Daniel J. , Brunel Nicolas
Published: October 2003

Recordings from cells in the associative cortex of monkeys performing visual working memory tasks link persistent neuronal activity, long‐term memory and associative memory. In particular, delayed pair‐associate tasks have revealed neuronal correlates of long‐term memory of associations between stimuli. Here, a recurrent cortical network model with Hebbian plastic synapses is subjected to the pair‐associate protocol. In a first stage, learning leads to the appearance of delay activity, representing individual images ('retrospective' activity). As learning proceeds, the same learning mechanism uses retrospective delay activity together with choice stimulus activity to potentiate synapses connecting neural populations representing associated images. As a result, the neural population corresponding to the pair‐associate of the image presented is activated prior to its visual stimulation ('prospective' activity). The probability of appearance of prospective activity is governed by the strength of the inter‐population connections, which in turn depends on the frequency of pairings during training. The time course of the transitions from retrospective to prospective activity during the delay period is found to depend on the fraction of slow, N‐methyl‐d‐aspartate‐like receptors at excitatory synapses. For fast recurrent excitation, transitions are abrupt; slow recurrent excitation renders transitions gradual. Both scenarios lead to a gradual rise of delay activity when averaged over many trials, because of the stochastic nature of the transitions. The model reproduces most of the neuro‐physiological data obtained during such tasks, makes experimentally testable predictions and demonstrates how persistent activity (working memory) brings about the learning of long‐term associations.
Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate‐induced seizures and expression in apoptotic neuronal cells
Authors: Condorelli Daniele F. , Trovato‐Salinaro Angela , Mudò Giuseppa , Mirone Melita B. , Belluardo Natale
Published: October 2003

The identification of connexins (Cxs) expressed in neuronal cells represents a crucial step for understanding the direct communication between neurons and between neuron and glia. In the present work, using a double‐labelling method combining in situ hybridization for Cx mRNAs with immunohistochemical detection for neuronal markers, we provide evidence that, among cerebral connexins (Cx26, Cx32, Cx36, Cx37, Cx40, Cx43, Cx45 and Cx47), only Cx45 and Cx36 mRNAs are localized in neuronal cells in both developing and adult rat brain. In order to establish whether connexin expression is influenced in vivo by abnormal neuronal activity, we examined the short‐term effects of kainate‐induced seizures. The results revealed an unexpected expression of Cx26 and Cx45 mRNA in neuronal cells undergoing apoptotic cell death in the CA3–CA4, in the hilus of the hippocampus and in other brain regions involved in seizure‐induced lesion. However, the expression of Cx26 and Cx45 mRNAs was not associated with detectable expression of corresponding proteins as evaluated by immunohistochemistry with specific antibodies. Moreover, in the same brain regions Cx32 and Cx43 were up‐regulated in non‐neruronal cells whereas the neuronal Cx36 was down‐regulated. Taken together the present results provide novel information regarding the specific subpopulation of neurons expressing Cx45 and raise the question of the meaning of connexin mRNA expression in the neuronal apoptotic process.
Increased neurogenesis and brain‐derived neurotrophic factor in neurokinin‐1 receptor gene knockout mice
Authors: Morcuende Sara , Gadd Christopher A. , Peters Marco , Moss Andrew , Harris Elizabeth A. , Sheasby Anne , Fisher Amy S. , De Felipe Carmen , Mantyh Patrick W. , Rupniak Nadia M. J. , Giese K. Peter , Hunt Stephen P.
Published: October 2003

It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain‐derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long‐term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin‐1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin‐1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin‐1 receptor knockout mice. Neurogenesis can be increased in wild‐type but not neurokinin‐1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain‐derived neurotrophic factor are also two‐fold higher in neurokinin‐1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus‐dependent learning and memory but found no clear enhancement in neurokinin‐1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain‐derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain‐derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.
Distribution of α‐ and γ‐synucleins in the adult rat brain and their modification by high‐dose cocaine treatment
Authors: Brenz Verca Maria S. , Bahi Amine , Boyer Frederic , Wagner George C. , Dreyer Jean‐Luc
Published: October 2003

Synucleins have attracted much attention because of their involvement in several neurodegenerative disorders. In a screening for genes differentially expressed after high‐dose cocaine exposure, we found γ‐synuclein as a major upregulated candidate in the tegmentum. Overexpression of both α‐ and γ‐synuclein after drug treatment was confirmed by means of microarrays, yielding an increase in the hippocampus, the striatum and the tegmentum (2.65 ×, 1.96 × and 3.5 ×, respectively, for α‐synuclein vs. 2.7 ×, 1.96 × and 7.16 × for γ‐synuclein), but no change in the nucleus accumbens. Investigation of the distribution of mRNA (byin situhybridization) and of the proteins (by immunocytochemistry) shows in both cases a clearly distinct pattern of expression for α‐ and γ‐synuclein. α‐synuclein displays a very characteristic distribution, confined to specific nuclei, whereas γ‐synuclein is more widely expressed throughout the brain. mRNA of both α‐ and γ‐synucleins display a complementary pattern of expression all over the cortex. In contrast to γ‐synuclein, α‐synuclein is neuronal, being only found in NeuN‐expressing cells, and is expressed in the basal ganglia (faintly) and in the substantia nigra compacta where it is highly correlated with tyrosine hydroxylase. Immunocytochemistry shows that γ‐synuclein generally colocalizes with glial fibrillary acidic protein‐expressing cells and is abundant in the red nucleus, the substantia nigra reticulata and the anterior commissure, while γ‐synuclein mRNA labels the matrix compartments of the caudate‐putamen. The role of synucleins in relation to cocaine‐induced plasticity or neurotoxicity is discussed.
Expression of PRiMA in the mouse brain: membrane anchoring and accumulation of ‘tailed’ acetylcholinesterase
Authors: Perrier Noël A. , Khérif Sonia , Perrier Anselme L. , Dumas Sylvie , Mallet Jacques , Massoulié Jean
Published: October 2003

We analysed the expression of PRiMA (proline‐rich membrane anchor), the membrane anchor of acetylcholinesterase (AChE), by in situ hybridization in the mouse brain. We compared the pattern of PRiMA transcripts with that of AChE transcripts, as well as those of choline acetyltransferase and M1 muscarinic receptors which are considered pre‐ and postsynaptic cholinergic markers. We also analysed cholinesterase activity and its molecular forms in several brain structures. The results suggest that PRiMA expression is predominantly or exclusively related to the cholinergic system and that anchoring of cholinesterases to cell membranes by PRiMA represents a limiting factor for production of the AChE tailed splice variant (AChET)–PRiMA complex, which represents the major AChE component in the brain. This enzyme species is mostly associated with cholinergic neurons because the pattern of PRiMA mRNA expression largely coincides with that of ChAT. We also show that, in both mouse and human, PRiMA proteins exist as two alternative splice variants which differ in their cytoplasmic regions.
Taste‐olfactory convergence, and the representation of the pleasantness of flavour, in the human brain
Authors: De Araujo Ivan E. T. , Rolls Edmund T. , Kringelbach Morten L. , McGlone Francis , Phillips Nicola
Published: October 2003

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher‐order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste–odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event‐related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.
5‐HT1A receptors are involved in short‐ and long‐term processes responsible for 5‐HT‐induced locomotor function recovery in chronic spinal rat
Authors: Antri M. , Mouffle C. , Orsal D. , Barthe J.‐Y.
Published: October 2003

After thoracic spinal cord transection, a paraplegic syndrome occurs. Previous data showed that an acute administration of a 5‐HT2 agonist (quipazine) could promote motor function recovery in spinal rats. However, continuous subdural perfusion of quipazine via an osmotic pump over 1 month proved to be more effective. The present study was designed to investigate the possible involvement of 5‐HT1A receptors in such recovery. Motor performances and locomotor parameters were analysed in spinal animals receiving daily, for 1 month, a dose of the 5‐HT1A agonist 8‐OHDPAT. The results were compared to those obtained in spinal rats receiving either a placebo or quipazine in the same conditions. Using daily injections instead of continuous perfusion of either receptor agonist to spinal animals allowed characterization of short‐ and long‐term consequences of pharmacological stimulation of 5‐HT1A and 5‐HT2 receptors on motor function recovery. Our data demonstrate that daily injections of a 5‐HT1A agonist induce long‐term, cumulative, positive effects on motor function recovery, as assessed by the improvement in the walking parameters observed before the ‘day‐test’ injection. This might involve use‐dependent processes depending on a chronic and/or repetitive stimulation of the spinal network for locomotion in relation to 5‐HT receptor activation. A further improvement in the motor parameters, transiently observed following the injection, suggests a more direct action of 5‐HT1A and 5‐HT2 receptor activation on spinal neurons involved in motor pattern generation.
Neurons of the rat preoptic area and the raphe pallidus nucleus innervating the brown adipose tissue express the prostaglandin E receptor subtype EP3
Authors: Yoshida Kyoko , Nakamura Kazuhiro , Matsumura Kiyoshi , Kanosue Kazuyuki , König Matthias , Thiel Heinz‐Jürgen , Boldogköi Zsolt , Toth Ida , Roth Joachim , Gerstberger Rüdiger , Hübschle Thomas
Published: October 2003

The major effector organ for thermogenesis during inflammation or experimental pyrogen‐induced fever in rodents is the brown adipose tissue (BAT). Prostaglandin E2 (PGE2) microinjection into the medial preoptic area (POA) of rats leads to hyperthermia through an increase in BAT thermogenesis and induces pyrogenic signal transmission towards the raphe pallidus nucleus (RPa), a brainstem nucleus known to contain sympathetic premotor neurons for BAT control. The medial POA has a high expression of prostaglandin E receptor subtype EP3 (EP3R) on POA neurons, suggesting that these EP3R are main central targets of PGE2 to mediate BAT thermogenesis. To reveal central command neurons that contain EP3R and polysynaptically project to the BAT, we combined EP3R immunohistochemistry with the detection of transneuronally labelled neurons that were infected after injection of pseudorabies virus into the BAT. Neurons double‐labelled with EP3R and viral surface antigens were particularly numerous in two brain regions, the medial POA and the RPa. Of all medial POA neurons that became virally infected 71 h after BAT inoculation, about 40% expressed the EP3R. This subpopulation of POA neurons is the origin of a complete neuronal chain that connects potential PGE2‐sensitive POA neurons with the BAT. As for the efferent pathway of pyrogenic signal transmission, we hypothesize that neurons of this subpopulation of EP3R expressing POA neurons convey their pyrogenic signals towards the BAT via the RPa. We additionally observed that two‐thirds of those RPa neurons that polysynaptically project to the interscapular BAT also expressed the EP3R, suggesting that RPa neurons themselves might possess prostaglandin sensitivity that is able to modulate BAT thermogenesis under febrile conditions.
Postsynaptic contributions to hippocampal network hyperexcitability induced by chronic activity blockade in vivo
Authors: Galvan Cynthia D. , Wenzel Jurgen H. , Dineley Kelly T. , Lam Trang T. , Schwartzkroin Philip A. , Sweatt J. David , Swann John W.
Published: October 2003

Neuronal activity is thought to play an important role in refining patterns of synaptic connectivity during development and in the molecular maturation of synapses. In experiments reported here, a 2‐week infusion of tetrodotoxin (TTX) into rat hippocampus beginning on postnatal day 12 produced abnormal synchronized network discharges in in vitro slices. Discharges recorded upon TTX washout were called ‘minibursts’, owing to their small amplitude. They were routinely recorded in area CA3 and abolished by CNQX, an AMPA receptor antagonist. Because recurrent excitatory axon collaterals remodel and glutamate receptor subunit composition changes after postnatal day 12, experiments examined possible TTX‐induced alterations in recurrent excitation that could be responsible for network hyperexcitability. In biocytin‐labelled pyramidal cells, recurrent axon arbors were neither longer nor more highly branched in the TTX infusion site compared with saline‐infused controls. However, varicosity size and density were increased. Whereas most varicosities contained synaptophysin and synaptic vesicles, many were not adjacent to postsynaptic specializations, and thus failed to form anatomically identifiable synapses. An increased pattern of excitatory connectivity does not appear to explain network hyperexcitability. Quantitative immunoblots also indicated that presynaptic markers were unaltered in the TTX infusion site. However, the postsynaptic AMPA and NMDA receptor subunits, GluR1, NR1 and NR2B, were increased. In electrophysiological studies EPSPs recorded in slices from TTX‐infused hippocampus had an enhanced sensitivity to the NR2B containing NMDA receptor antagonist, ifenprodil. Thus, increases in subunit protein result in alterations in the composition of synaptic NMDA receptors. Postsynaptic changes are likely to be the major contributors to the hippocampal network hyperexcitability and should enhance both excitatory synaptic efficacy and plasticity.
The cerebellum and spatial ability: dissection of motor and cognitive components with a mouse model system
Authors: Martin Loren A. , Goldowitz Dan , Mittleman Guy
Published: October 2003

The cerebellum has recently been linked to spatial navigation, as indicated by the inferior performance of cerebellar mutant or cerebellar lesioned animals in the water maze. The inability to dissociate motor from cognitive deficits in the impaired water maze performance has been a confounding variable in previous studies, however. In this study, we sought to define clearly the role of the cerebellar system in spatial navigation outside of motor control by creating a mouse model of Purkinje cell loss with intact motor ability, and testing these mice in the water maze. To this end, we made aggregation chimeras between Lc/+ mice, which lose all Purkinje cells postnatally, and +/+ control mice. Lc/+ mice are ataxic and show impaired rotor‐rod performance. By contrast, we show that Lc/+ ⇆ +/+ chimeras above a threshold of Purkinje cell loss show no outward signs of motor impairment and demonstrated normal rotor‐rod ability. In the water maze, we found that Lc/+ mice showed impaired performance in the place, cue and platform removal tasks, whereas Lc/+⇆+/+ chimeras performed similarly to controls in all tasks. We found that the impaired performance in the water maze of Lc/+ mice resulted from both motor as well as cognitive impairment that could be separated from one another by statistical means. In addition, through the analysis of individual chimeric mice, the relationships between these deficits and the total number of Purkinje cells were determined and a specific role for Purkinje cells in search strategy was identified.
Distinct subtypes of group I metabotropic glutamate receptors on rat spinal neurons mediate complex facilitatory and inhibitory effects
Authors: Marchetti Cristina , Taccola Giuliano , Nistri Andrea
Published: October 2003

While group I glutamate metabotropic (mGlu) receptors show discrete neuronal distribution in the neonatal rat spinal cord, the functional role of their distinct receptor subtypes remains uncertain. Intracellular recording from lumbar motoneurons together with extracellular recording of ventral root (VR) responses was used to investigate the differential contribution by mGlu receptor subtypes to cell excitability and network activity. The group I agonist DHPG evoked motoneuron depolarization (via the AIDA or CPCCOEt‐sensitive mGlu receptor subtype 1) mainly at network level and generated sustained, network‐dependent oscillations (via the MPEP‐sensitive mGlu receptor subtype 5). DHPG also decreased the peak amplitude of synaptic responses induced by dorsal root stimuli, an effect unrelated to depolarization and dependent on glycinergic transmission. Synaptic responses were insensitive to AIDA or MPEP. The present results can be explained by assuming excitation of discrete classes of interneurons by group I mGlu receptor activity. Thus, the cellular distribution of those mGlu receptors at strategic circuit connections may determine the functional outcome of the network in terms of excitation or inhibition. Even if there was insufficient activation by endogenous glutamate of mGlu receptors during synaptic activity evoked by DR stimuli, it is apparent that such receptors are important pharmacological targets for powerful and rapid up‐ or down‐regulation of spinal signal processing at network level, providing a rationale for the proposed use of mGlu receptor agonists in a variety of spinal pathological conditions.
Subthalamic stimulation influences postmovement cortical somatosensory processing in Parkinson's disease
Authors: Devos D. , Labyt E. , Cassim F. , Bourriez J. L. , Reyns N. , Touzet G. , Blond S. , Guieu J. D. , Derambure P. , Destée A. , Defebvre L.
Published: October 2003

In Parkinson's disease, poor motor performance (resulting primarily from abnormal cortical activation during movement preparation and execution) may also be due to impaired sensorimotor integration and defective cortical activity termination of the ongoing movement, thus delaying preparation of the following one. Reduced movement‐related synchronization of the beta rhythm in Parkinson's disease compared to controls has been put forward as evidence for impaired postmovement cortical deactivation. We assessed the effects of subthalamic deep brain stimulation and l‐dopa on beta rhythm synchronization over the premotor and primary sensorimotor cortex. Ten advanced patients performed self‐paced wrist flexion in four conditions according to the presence or not of stimulation and l‐dopa. Compared to without treatment, the motor score improved by ≈ 60%; the beta synchronization was present over the contralateral frontocentral region and increased significantly over the contralateral central region under stimulation and under l‐dopa, with a maximal effect when both treatments were associated. Our advanced patients displayed very focused and attenuated beta rhythm synchronization which, under stimulation, increased over the contralateral premotor and primary sensorimotor cortex. Stimulation and l‐dopa both partly restored postmovement cortical deactivation in advanced Parkinson's disease, although the respective mechanisms probably differ. They may improve bradykinesia and cortical deactivation by reestablishing movement‐related somatosensory processing at the end of the movement through the basal ganglia into the cortex.
Recombinant AAV‐mediated expression of galanin in rat hippocampus suppresses seizure development
Authors: Lin En‐Ju D. , Richichi Cristina , Young Deborah , Baer Kristin , Vezzani Annamaria , During Matthew J.
Published: October 2003

Galanin, a 29‐ or 30‐amino acid neuropeptide, has been implicated in the modulation of seizures. In this study, we constructed a recombinant adeno‐associated viral (AAV) vector to constitutively over‐express galanin (AAV‐GAL). The vector mediated efficient transduction of HEK 293 cells in vitro and robust galanin expression in vivo when injected into the rat dorsal hippocampus. Rats were administered kainic acid intrahippocampally 2.5 months following AAV‐GAL or empty vector (AAV‐Empty) injection to study the effect of vector‐mediated galanin over‐expression on seizures. AAV‐GAL‐injected rats showed a decreased number of seizure episodes and total time spent in seizures compared to AAV‐Empty rats, despite similar latencies to development of the first EEG seizure and similar levels of neuronal damage in the CA3 region for both groups. These data show that recombinant AAV mediates strong and stable over‐expression of galanin when injected into the rat hippocampus resulting in a significant anticonvulsive effect. The seizure suppression effect of galanin expression in the hippocampus by viral vectors may lead to novel therapeutic strategies for the treatment and management of intractable seizures with focal onset such as temporal lobe epilepsy.
Age‐related modifications of the morphological organization of pituicytes are associated with alteration of the GABAergic and dopaminergic innervation afferent to the neurohypophysial lobe
Authors: Alonso G. , Runquist M. , Hussy N. , Duvoid A. , Moos F.
Published: October 2003

Ageing is known to induce a marked activation of astrocytes within various regions of the central nervous system. To date, the age‐related factors responsible for these modifications are unknown.The neural lobe of the hypophysis (NL) is a particular brain region which does not contain neurons but does contain specialized astrocytes, called pituicytes, and numerous terminals of afferent axons, including (i) peptidergic neurohypophysial axons which terminate on the NL blood vessels, and (ii) axons containing both gamma amino‐butyric acid (GABA) and dopamine (DA) which form contacts with pituicytes. Because evidence has recently been provided that GABA signalling mediates the morphological organization of astrocytes, the present study was designed to determine whether modifications of pituicytes during ageing were associated with modifications of the GABAergic axons innervating the NL. We show here that, in adult rats, GABA/DA axons form preferential synaptic‐like contacts with pituicytes which express both GABAA and D2 dopamine receptors. We then show that, during ageing, pituicytes undergo dramatic modifications of their morphology, correlatively with marked modifications of the GABA/DA fibres innervating the NL. Lastly, in vitro experiments indicate that modifications of the morphology of pituicytes similar to those observed during ageing were obtained by incubating isolated NL of adult rats with a GABAA receptor agonist and/or a D2 dopamine receptor antagonist, whereas inverse modifications were observed when NL of aged rats were incubated with a GABAA receptor antagonist and a D2 dopamine receptor agonist. Taken together, these data suggest that the age‐related morphological changes of pituicytes result from the alteration of the GABA/DAergic innervation of the NL.
Age‐related changes in the dynamics of human albino visual pathways
Authors: Neveu Magella M. , Jeffery Glen , Burton Linda C. , Sloper John J. , Holder Graham E.
Published: October 2003

A deficiency of melanin in the retinal pigment epithelium, which regulates the development of neural retina, leads to chiasmal misrouting such that the uncrossed pathway (to the ipsilateral hemisphere) is reduced relative to the crossed pathway (to the contralateral hemisphere). This study examines age‐related changes in the flash and pattern appearance visual evoked potentials (VEP) of human albinos. Scalp recorded cortical VEPs to flash (FVEP) and pattern appearance stimulation were recorded in 58 albino (8 months to 60 years) and 34 normal subjects (4–55 years). VEPs were analysed by amplitude and latency. The contralateral hemisphere FVEP amplitude decreased with age in albino subjects, as in both hemispheres in normals. However, the ipsilateral hemisphere FVEP amplitude was significantly lower in young albino subjects, initially giving a marked interhemispheric asymmetry, but this normalized with age. Significant interhemispheric FVEP latency asymmetries were not observed. The contralateral pattern appearance VEP latency in albino subjects decreased with age, as in both hemispheres in normals; the ipsilateral latency increased significantly with age. Significant interhemispheric pattern appearance VEP amplitude asymmetries were not observed. These novel and unexpected observations indicate significant age‐related changes in the retinocortical pathways of the human albino. These changes have implications for our understanding of development and plasticity of the central visual pathways.
The coding of odour‐intensity in the honeybee antennal lobe: local computation optimizes odour representation
Authors: Sachse Silke , Galizia C. Giovanni
Published: October 2003

We investigated strategies involved in odour intensity coding by the primary olfactory centre of insects, the antennal lobe (AL), the structural and functional analogue of the olfactory bulb. Using calcium imaging in the honeybee, we simultaneously measured the projection neuron output responses and a compound signal dominated by receptor neuron input in identified olfactory glomeruli to odours spanning seven log units of concentration. A comparison of the two processing levels indicates that the intercellular computation within the AL modulates and contrast‐enhances the primary olfactory signals. As a result the AL network optimizes the olfactory code: odour representation is improved at lower concentrations, the relative activity of olfactory glomeruli allows encoding odour quality over up to four log‐unit concentrations, and odour‐intensity is reliably represented in the overall excitation across AL.
The medial prefrontal cortex differentially regulates stress‐induced c‐fos expression in the forebrain depending on type of stressor
Authors: Figueiredo Helmer F. , Bruestle Amy , Bodie Bryan , Dolgas Charles M. , Herman James P.
Published: October 2003

The medial prefrontal cortex (mPFC) plays an important inhibitory role in the hypothalamic‐pituitary‐adrenal (HPA) axis response. The involvement of the mPFC appears to depend on the type of stressor, preferentially affecting ‘psychogenic’ stimuli. In this study, we mapped expression of c‐fos mRNA to assess the neural circuitry underlying stressor‐specific actions of the mPFC on HPA reactivity. Thus, groups of mPFC‐lesioned and sham‐operated rats were restrained for 20 min or exposed to ether fumes for 2 min. In both cases, the animals were killed at 40 min from the onset of stress. Interestingly, bilateral lesions of the mPFC significantly enhanced c‐fos mRNA expression in the hypothalamic paraventricular nucleus of restrained animals, an effect that was paralleled by potentiation of circulating ACTH concentrations in these animals. On the other hand, lesions of the mPFC did not affect neither PVN c‐fos mRNA expression nor plasma ACTH concentrations in animals exposed to ether. Lesions of the mPFC also enhanced c‐fos activation in the medial amygdala following restraint, but not following ether exposure. Additional regions whose activity was affected by mPFC lesions or stressor differences included the ventrolateral division of the bed nucleus of the stria terminalis, CA3 hippocampus, piriform cortex, and dorsal endopiriform nucleus. Expression of c‐fos mRNA was nearly absent in the central amygdala of all stressed animals, regardless of lesion. Furthermore, prefrontal cortex lesions did not change stress‐induction levels of c‐fos in the CA1 hippocampus, dentate gyrus, anteromedial division of the bed nucleus of the stria terminalis, lateral septum, and claustrum. Taken together, this study indicates that the medial prefrontal cortex differentially regulates cellular activation of specific stress‐related brain regions, thus exerting stressor‐dependent inhibition of the HPA axis.
Contribution of Kir3.1, Kir3.2A and Kir3.2C subunits to native G protein‐gated inwardly rectifying potassium currents in cultured hippocampal neurons
Authors: Leaney Joanne L.
Published: October 2003

G protein‐gated inwardly rectifying potassium (GIRK) channels are found in neurons, atrial myocytes and neuroendocrine cells. A characteristic feature is their activation by stimulation of Gi/o‐coupled receptors. In central neurons, for example, they are activated by adenosine and GABA and, as such, they play an important role in neurotransmitter‐mediated regulation of membrane excitability. The channels are tetrameric assemblies of Kir3.x subunits (Kir3.1–3.4 plus splice variants). In this study I have attempted to identify the channel subunits which contribute to the native GIRK current recorded from primary cultured rat hippocampal pyramidal neurons. Reverse transcriptase–polymerase chain reaction revealed the expression of mRNA for Kir3.1, 3.2A, 3.2C and 3.3 subunits and confocal immunofluorescence microscopy was used to investigate their expression patterns. Diffuse staining was observed on both cell somata and dendrites for Kir3.1 and Kir3.2A yet that for Kir3.2C was weaker and punctate. Whole‐cell patch clamp recordings were used to record GIRK currents from hippocampal pyramidal neurons which were identified on the basis of inward rectification, dependence of reversal potential on external potassium concentration and sensitivity to tertiapin. The GIRK currents were enhanced by the stimulation of a number of Gi/o‐coupled receptors and were inhibited by pertussis toxin. In order to ascertain which Kir3.x subunits were responsible for the native GIRK current I compared the properties with those of the cloned Kir3.1 + 3.2A and Kir3.1 + 3.2C channels heterologously expressed in HEK293 cells.
Involvement of transient receptor potential‐like channels in responses to mGluR‐I activation in midbrain dopamine neurons
Authors: Tozzi Alessandro , Bengtson C. Peter , Longone Patrizia , Carignani Corrado , Fusco Francesca R. , Bernardi Giorgio , Mercuri Nicola B.
Published: October 2003

We investigated the involvement of store‐operated channels (SOCs) and transient receptor potential (TRP) channels in the response to activation of the group I metabotropic glutamate receptor subtype 1 (mGluR1) with the agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG, puff application) in dopamine neurons in rat brain slices. The mGluR1‐induced conductance reversed polarity close to 0 mV and at more positive potentials when extracellular potassium concentrations were increased, indicating the involvement of a cationic channel. DHPG currents but not intracellular calcium responses were reduced by low extracellular sodium concentrations but were not affected by sodium channel blockers, tetrodotoxin and saxitoxin or by inhibition of the h‐current with cesium. Abolition of calcium responses with intracellular BAPTA (1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid; 10 mm) did not affect current responses, indicating they were not calcium activated. Extracellular application of non‐selective SOCs and TRP channel blockers 2‐aminoethoxydiphenylborane (2‐APB), SKF96365, ruthenium red and flufenamic acid (but not gadolinium) reduced DHPG current and calcium responses. Intracellular application of ruthenium red and 2‐APB did not affect DHPG currents, indicating that IP3 and ryanodine receptors did not mediate their actions. Single‐cell PCR revealed the presence of TRPC1 and 5 mRNA in most dopamine neurons and subtypes 3, 4 and 6 in some. Store depletion evoked calcium entry indicative of SOCs, providing the first functional observation of such channels in native central neurons. Store depletion with either cyclopiazonic acid or ryanodine abolished calcium but not current responses to DHPG. The electrophysiological and pharmacological properties of the mGluR1‐induced inward current are consistent with the involvement of TRP channels whereas calcium responses are dependent on the function of SOCs in voltage clamp recordings.
Attention capture by auditory significant stimuli: semantic analysis follows attention switching
Authors: Escera Carles , Yago Elena , Corral Maria‐José , Corbera Sílvia , Nuñez M. Isabel
Published: October 2003

Event‐related potentials (ERPs) were recorded from the scalp to investigate a long‐standing controversy in auditory attention research, namely when the ‘breakthrough of the unattended’ takes place in the human brain. Nine subjects classified visual stimuli appearing 300 ms after task‐irrelevant standard tones (80%, i.e. P = 0.8) or novel sounds (20%, i.e. P = 0.2) into odd/even categories. After the recording session, subjects scored the novel sounds as to whether they had any particular meaning (identifiable) or were perceived as a burst of noise (non‐identifiable), and performance and ERPs were analysed according to this classification. A control condition, in which the visual stimuli were presented with no sounds, showed that subjects covertly monitored the task‐irrelevant sounds during visual task‐performance, and a further condition, in which the auditory and visual stimuli appeared regardless of each other, made it possible to trace the processing of the distracters during allocation of attention outside the auditory environment. Results yielded identical N1‐enhancement for the two types of novel sounds, indicating similar attention switching triggered to these two types of unexpected sounds. However, there was a stronger orientating of attention towards identifiable novel sounds, as indicated both by behavioural distraction and by larger novelty‐P3. Furthermore, this stronger orientating of attention was due to the sounds being contingent on the visual stimuli, as no increase in novelty‐P3 to identifiable novel sounds was observed in the control condition, in which the sounds occurred outside the attentional set. Therefore, provided that the N1‐enhancement reflects a call for focal attention, and novelty‐P3 the effective orientating of attention towards the eliciting sounds, the present results suggest that semantic analysis of significant sounds occurs after a transitory switch of attention towards the eliciting stimuli. Moreover, as the novelty‐P3 increase in amplitude was observed only when subjects covertly monitored the sounds, the present data suggest that semantic analysis of irrelevant sounds depends on the top‐down cognitive influences of the attentional set.
Distinct roles of the different ionotropic glutamate receptors within the nucleus accumbens in passive‐avoidance learning and memory in mice
Authors: De Leonibus Elvira , Costantini Vivian J. A. , Castellano Claudio , Ferretti Valentina , Oliverio Alberto , Mele Andrea
Published: October 2003

Research on the role of the nucleus accumbens in behaviour has been largely focused on the functions of this structure in conditioning to appetitive stimuli. It has been suggested that a network comprising the nucleus accumbens and its convergent inputs might mediate dissociable functions in the acquisition, the consolidation and the retrieval of information. However, findings related to a role of this structure in aversive conditioning are somewhat contradictory, and its involvement in this form of learning is still under debate. Moreover, very little evidence is available on the step of information processing mediated by the accumbens. Thus the purpose of this study was to investigate the effects of the blockade of the AMPA and NMDA glutamate receptors, which have been suggested to mediate the transmission of information from the limbic system to this structure, on a classical aversive conditioning task – the one‐trial step through inhibitory avoidance paradigm (24 h interval between training and testing). Intra‐accumbens focal injections of AP‐5 and DNQX (NMDA and AMPA antagonists, respectively) were performed immediately after training, before training and before testing in mice. The NMDA antagonist (37.5, 75 and 150 ng per side) impaired animal performance only if administered immediately after but not before training or before testing. Conversely, DNQX (0.5, 1.0 and 5.0 ng per side) reduced the step through latencies when administered before training and before testing. These findings suggest that NMDA receptor activation within the accumbens is necessary in formation but not expression of memory for inhibitory avoidance. AMPA receptors, instead, are necessary for the acquisition and the expression but not consolidation of inhibitory avoidance memory.
Selective psychostimulant sensitization by food restriction: differential changes in accumbens shell and core dopamine
Authors: Cadoni Cristina , Solinas Marcello , Valentini Valentina , Di Chiara Gaetano
Published: October 2003

We have recently reported that behavioural sensitization to morphine, amphetamine, cocaine and nicotine is associated with an increased response of dialysate dopamine to the same drugs in the nucleus accumbens core and/or a reduced response in the shell. Prolonged exposure to stressful stimuli also induces behavioural sensitization to drugs of abuse. We therefore investigated the effect of different drugs of abuse on behaviour and on dopamine transmission in the nucleus accumbens shell and core of rats stressed by 1 week schedule of food restriction. Food‐restricted rats (80% of their initial body weight) were implanted with microdialysis probes in the nucleus accumbens shell and core and challenged with cocaine (5 and 10 mg/kg i.p.), amphetamine (0.25 and 0.5 mg/kg s.c.), morphine (1 and 2 mg/kg s.c.), nicotine (0.2 and 0.4 mg/kg s.c.) and the changes in dialysate dopamine transmission were monitored together with the behaviour. Food restricted rats showed strong behavioural sensitization to cocaine and amphetamine but not to morphine or nicotine as compared to ad libitum fed controls. Behavioural sensitization to psychostimulants was associated with an increased response of dialysate dopamine in the core and with an unchanged or even reduced response in the shell. No significant differences were observed between controls and food‐restricted animals in the ability of morphine and nicotine to stimulate dopamine transmission in the shell and core. The present results indicate that a sensitized dopamine response in the nucleus accumbens core is a general feature of the expression of behavioural sensitization.