bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Pathway From the Reticular and Perireticular Nuclei to the Thalamus in Ferrets: A Dil Study
Authors: Mitrofanis John
Published: April 2006

This study examines the connections of the thalamic reticular and perireticular cell groups in developing ferrets. Small crystals of Dil (1,1′‐dioctadecyl‐3, 3, 3′, 3′‐tetramethylindocarbocyanine perchlorate) were implanted into either the dorsal thalamus or the cerebral cortex of aldehyde‐fixed prenatal and postnatal ferret brains. A small implant of Dil into the presumptive lateral geniculate nucleus during early prenatal development [between embryonic day 23 (E23) and E25] reveals many retrogradely labelled cells in the reticular nucleus. At E40, just before birth, the number of cells retrogradely labelled in the reticular nucleus has become reduced compared to earlier prenatal implants, whether from small or large implants of Dil into the lateral geniculate nucleus. By postnatal day 7, an adult‐like pattern of retrograde labelling is seen in the reticular nucleus; at this age, a small implant of Dil limited to the lateral geniculate nucleus retrogradely labels a discrete group of cells located in the caudal regions of the reticular nucleus. In the internal capsule, adjacent to the reticular nucleus, there are two distinct groups of neurons. One group, called the large‐celled perireticular zone (LPR), enters the internal capsule very early in development (from E25; Mitrofanis, J., Eur. J. Neurosci., 6, 253–263, 1994) and is not labelled from the lateral geniculate nucleus at any developmental stage. Small implants of Dil into presumptive visual and somatosensory cortices shows that the LPR lies in a distinct region of the primordial internal capsule. Corticothalamic and thalamocortical axons turn sharply in the region of the LPR, whilst corticospinal and corticobulbar axons pass straight through the LPR on towards their more caudal targets. Later, after both sets of axons have reached their targets, the LPR is not seen in the internal capsule. The other group of cells in the internal capsule, called the small‐celled perireticular zone (SPR), forms a distinct band of cells lying midway between the reticular nucleus and the globus pallidus. These cells enter the internal capsule much later in development, at about E40. Unlike the cells in the LPR, cells in the SPR are retrogradely labelled after an implant of Dil into the lateral geniculate nucleus, and there are many which remain in the adult (Clemence, A. E. and Mitrofanis, J., J. Comp. Neurol., 322, 167–181, 1992).
Distribution of Somatostatin Receptors 1, 2 and 3 mRNA in Rat Brain and Pituitary
Authors: Señarís R. M. , Humphrey P. P. A. , Emson P. C.
Published: April 2006

In this study sequence‐specific antisense oligonucleotide probes have been used to investigate the distribution of the mRNAs coding for the somatostatin receptor subtypes termed somatostatin receptor 1, somatostatin receptor 2 and somatostatin receptor 3 in the rat brain and pituitary using in situ hybridization techniques. The three receptor subtype mRNAs were found to be widely distributed in the brain with different patterns of expression, but with some overlap. Somatostatin receptor 1 mRNA was particularly concentrated in the cerebral and piriform cortex, magnocellular preoptic nucleus, hypothalamus, amygdala, hippocampus, and several nuclei of the brainstem. Somatostatin receptor 3 mRNA was very abundant in the cerebellum and pituitary (in contrast to somatostatin receptor 1), but it was also found in hippocampus, amygdala, hypothalamus and in motor nuclei of the brainstem. Somatostatin receptor 2 mRNA levels were very low relative to the other two mRNAs evaluated. Receptor 2 mRNA was observed in the anterior pituitary, and in the brain it was found in the medial habenular nucleus, claustrum, endopiriform nucleus, hippocampus, some amygdala nuclei, cerebral cortex and hypothalamus. None of the three somatostatin receptor mRNAs studied here was found in the caudate nucleus. Northern analysis revealed distinct sizes of mRNAs for each subtype, and displacement experiments showed that each probe sequence was subtype‐specific.
Peripheral and Central Mechanisms of NGF‐induced Hyperalgesia
Authors: Lewin Gary R. , Rueff Alain , Mendell Lorne M.
Published: April 2006

Mechanisms underlying the hyperalgesia induced by a single systemic injection of nerve growth factor (NGF) in adult rats were studied in vivo. A single dose of NGF initiated a prolonged thermal hyperalgesia to a radiant heat source within minutes that lasted for days. Animals which had been pretreated with the mast cell degranulating compound 48/80 or either one of two specific 5‐hydroxytryptamine receptor antagonists (ICS 205–930 and methiothepin) also developed an NGF‐induced thermal hyperalgesia, but onset was delayed by more than 3 h. In the presence of ICS 205‐930 or methiothepin the early component NGF‐induced hyperalgesia was reversed and the animals responded with an initial hypoalgesia to the thermal stimuli. Whereas these results indicate a peripheral mechanism for the initial thermal hyperalgesia, the later phase (7 h–4 days after NGF) appeared to be centrally maintained, since it could be selectively blocked by the non‐competitive NMDA receptor antagonist MK‐801. In contrast to the almost immediate thermal hyperalgesia following a single injection of NGF, a significant mechanical hyperalgesia began only after a 7 h latency. This NGF‐induced mechanical hyperalgesia was not blocked by any of the treatments that attenuated the thermal hyperalgesia, indicating that a separate mechanism may be involved. Additional electrophysiological experiments showed that NGF‐induced hyperalgesia was not maintained by an increased amount of spontaneous activity in C‐fibres. A final result showed that endogenous release of NGF in a model of acute inflammation (complete Freund's adjuvant‐induced inflammation) may be involved in the development of thermal hyperalgesia, since it could be blocked by concomitant treatment with anti‐NGF antisera. These data indicate that NGF‐induced thermal and mechanical hyperalgesia are mediated by different mechanisms. The rapid onset component of thermal hyperalgesia is due to a peripheral mechanism involving the degranulation of mast cells, whereas the late component involves central NMDA receptors. In contrast, the NGF‐induced mechanical hyperalgesia seems to be independent of mast cell degranulation or central NMDA receptor sites.
REVIEW
Authors: Obeso J. A. , Grandas F. , Herrero M. T. , Horowski R.
Published: April 2006

More effective measures to control and replace the dopaminergic deficit of Parkinson's disease are being actively sought. One basic problem is how the striatal dopamine loss should be replaced in order to mimic most accurately the physiological state. Animal electrophysiology indicates that the dopaminergic nigrostriatal pathway has a dual tonic and phasic action. Intermittent dopaminergic stimulation is associated with behavioural hyposensitivity both in animal models and in patients with Parkinson's disease. Continuous dopaminergic stimulation provides a tonic background and improves some clinical problems but is also associated with tolerance. None of the available pharmacological approaches can restore the dopamine deficiency of Parkinson's disease to physiological levels. Continuous dopaminergic stimulation for <24 h, associated with small doses of levodopa or a short‐acting dopamine agonist, appears to be the best, albeit imperfect, therapeutic approach until other, more efficacious remedies are developed.
Computational Structure of Visual Callosal Axons
Authors: Innocenti Giorgio M. , Lehmann Patricia , Houzel Jean‐Christophe
Published: April 2006

We analysed the activation profiles obtained by simulating invasion of an orthodromic action potential in eleven anterogradely filled and serially reconstructed terminal arbors of callosal axons originating and terminating in areas 17 and 18 of the adult cat. This was done in order to understand how geometry relates to computational properties of axons. In the simulation, conduction from the callosal midline to the first bouton caused activation latencies of 0.9‐3.2 ms, compatible with published electrophysiological values. Activation latencies of the total set of terminal boutons varied across arbors between 0.3 and 2.7 ms. Arbors distributed boutons in tangentially segregated terminal columns spanning one or, more often, several layers. Individual columns of one axon were frequently activated synchronously or else within a few hundred microseconds of each other. Synchronous activation of spatially separate columns is achieved by: (i) long primary or secondary branches of similar calibre running nearly parallel to each other for several millimetres; (ii) variations in the calibre of branches serially fed to separate columns by the same primary or secondary branch; (iii) exchange of high‐order or preterminal branches across columns. The long, parallel branches blatantly violate principles of axonal economy. Simulated alterations of the axonal arbors indicate that similar spatiotemporal patterns of activity could, in principle, be obtained by less axon‐costly architectures. The structure of axonal arbors, therefore, may not be determined solely by the type of spatiotemporal activation profiles it achieves in the cortex but also by other constraints, in particular those imposed by developmental mechanisms.
Differential Expression of Two Glial Glutamate Transporters in the Rat Brain: an In Situ Hybridization Study
Authors: Torp R. , Danbolt N. C. , Babaie E. , BjØrås M. , Seeberg E. , Storm‐Mathisen J. , Ottersen O. P.
Published: April 2006

The distributions of the mRNAs encoding the l‐glutamate transporters GLT1 and GLAST were examined in the rat brain by in situ hybridization using 35S‐labelled oligonucleotide probes. Probes directed to GLT1 produced dense labelling in the hippocampus, neocortex and neostriatum, and weak labelling in the cerebellum. In contrast, GLAST mRNA appeared to be greatly enriched in the cerebellum compared to other brain regions. While the intensity of the labelling for GLAST and GLT1 varied among different regions, their cellular distributions appeared to coincide inasmuch as both mRNAs were mainly expressed by glial cells. Labelling occurred, inter alia, in glial cells throughout the hippocampus, and in Golgi epithelial cells in the Purkinje cell layer of the cerebellum.
Calcium Channel Currents in Undifferentiated Human Neuroblastoma (SH‐SY5Y) Cells: Actions and Possible Interactions of Dihydropyridines and ω‐Conotoxin
Authors: Reeve Helen L. , Vaughan Peter F. T. , Peers Chris
Published: April 2006

Ca2+ channel currents were recorded in undifferentiated human neuroblastoma (SH‐SY5Y) cells with the whole‐cell patch‐clamp technique, using 10 mM Ba2+ as charge carrier. Currents were only evoked by depolarizations to ‐30 mV or more positive (holding potential ‐80 mV), inactivated partially during 200 ms depolarizing steps, and were abolished by 150 μMCd2+. Currents could be enhanced by Bay K‐8644 and partially inhibited by nifedipine, suggesting that they arose in part due to activation of L‐type Ca2+ channels. Currents were also inhibited by the marine snail peptide ω‐conotoxin GVIA (ω‐CgTx). At a concentration of 10 nM inhibition by ω‐CgTx was reversible, but at higher concentrations blockade was always irreversible. Although current inhibition by nifedipine was maximal at 1μM, supramaximal concentrations reduced the inhibitory actions of ω‐CgTx in a concentration‐dependent manner. Ca2+ channel currents evoked from a holding potential of ‐50 mV showed no inactivation during 200 ms depolarizations but declined in amplitude with successive depolarizing steps (0.2 Hz). Current amplitudes could be restored by returning the holding potential to ‐80 mV. Currents evoked from ‐50 mV were inhibited by nifedipine and ω‐CgTx to a similar degree as those evoked from ‐80 mV. Our results indicate that undifferentiated SH‐SY5Y cells possess L‐ and N‐type Ca2+ channels which can be distinguished pharmacologically but cannot be separated by using depolarized holding potentials. Furthermore, these data suggest that nifedipine has a novel action to inhibit blockade of N‐type channels by ω‐CgTx.
Electrophysiological Interactions Between 5‐Hydroxytryptamine and Thyrotropin Releasing Hormone on Rat Hippocampal CA1 Neurons
Authors: Ballerini L. , Corradetti R. , Nistri A. , Pugliese A. M. , Stocca G.
Published: April 2006

Intracellular recording from CA1 neurons of the rat hippocampal slice preparation was used to examine the possibility of functional interactions between 5‐hydroxytryptamine (5‐HT) and thyrotropin releasing hormone (TRH), which act as cotransmitters in other areas of the central nervous system. 5‐HT (30 μM) elicited complex effects consisting of biphasic changes in membrane potential and a strong depression of the afterhyperpolarization (AHP) following a spike burst. TRH (10 μM) did not alter membrane potential or input conductance but it produced a partial block of the AHP. Under single‐electrode voltage clamp, 5‐HT and TRH both reduced the amplitude of voltage‐activated total K+ currents. When the two substances were co‐applied, their actions were occluded. The voltage‐activated K+ current remaining in Ca2+‐free solution lost its sensitivity to 5‐HT and TRH, suggesting that the K+ current modulated by TRH and 5‐HT was Ca2+‐dependent, although TRH itself did not depress high‐threshold voltage‐activated Ca2+ currents. When a relatively small concentration (5 μM) of 5‐HT was co‐applied with an equimolar amount of TRH, the degree of block of the spike AHP was the sum of the two individual effects of these drugs. It is suggested that in hippocampal pyramidal cells 5‐HT and TRH influenced neuronal excitability by depressing a Ca2+‐dependent K+ current, a phenomenon perhaps mediated through a common intracellular second messenger pathway.
Muscarinic Modulation of Intrinsic Burst Firing in Rat Hippocampal Neurons
Authors: Azouz Rony , Jensen Morten S. , Yaari Yoel
Published: April 2006

Intracellular recordings in rat hippocampal slices were used to examine how exogenous and endogenous cholinergic agonists modulate the firing pattern of intrinsically burst‐firing pyramidal cells. About 24% of CA1 pyramidal cells generated all‐or‐none, high‐frequency bursts of fast action potentials in response to intracellular injection of long positive current pulses. Application of carbachol (5 μM) converted burst firing in these neurons into regular trains of independent spikes. Acetylcholine (5 μM) exerted a similar effect, provided acetylcholine esterase activity was blocked with neostigmine (2 μM). Atropine (1 μM) reversed this cholinergic effect, indicating its mediation by muscarinic receptors. Cholinergic agonists also caused mild neuronal depolarization but the block of intrinsic burst firing was independent of this effect. Repetitive stimulation of cholinergic fibres in the presence of neostigmine (2 μM) evoked a slow cholinergic excitatory postsynaptic potential (EPSP) lasting about a minute. During the slow EPSP, burst firing could not be evoked by depolarizing pulses and the neurons fired in regular mode. These effects were prevented by pretreatment with atropine (1 μM). Exogenously applied cholinergic agonists and endogenously released acetylcholine also reduced spike frequency accommodation and suppressed the long‐duration afterhyperpolarization in burst‐firing pyramidal cells in an atropine‐sensitive manner. A membrane‐permeable cAMP analogue (8‐bromo‐cAMP; 1 mM) also reduced frequency accommodation and blocked the long‐duration afterhyperpolarization, but did not affect intrinsic burst firing at all. Taken together, the data show that muscarinic receptor stimulation transforms the stereotyped, phasic response of burst‐firing neurons into stimulus‐graded, tonic discharge.
Depth Perception in Monocularly Deprived Cats Following Part‐time Reverse Occlusion
Authors: Mitchell Donald E. , Ptito Maurice , Lepore Franco
Published: April 2006

The behavioural effects of an early period of monocular deprivation can be extremely profound. However, it is possible to achieve a high degree of recovery, even to normal levels of visual acuity, by prompt imposition of certain regimes of part‐time reverse occlusion where the initially non‐deprived eye is occluded for only part of each day in order to allow a daily period of binocular visual exposure. In this paper we report on the depth perception of five monocularly deprived cats that had recovered normal visual acuity in both eyes following imposition of certain of the above occlusion regimes. Although three of the animals exhibited five‐to sevenfold superiority of binocular over monocular depth thresholds, subsequent tests made on two of the animals revealed that they were unable to make stereoscopic discriminations with random‐dot stereograms. Despite the recovery of normal visual acuity in both eyes, we conclude that these animals recover at best only local stereopsis.
Cortical Cells That Migrate Beyond Area Boundaries: Characterization of an Early Neuronal Population in the Lower Intermediate Zone of Prenatal Rats
Authors: DeDiego Isabel , Smith‐Fernández Anibal , Fairén Alfonso
Published: April 2006

Studies of the early development of the mammalian cerebral cortex have revealed that the earliest generated neurons that form the primordial plexiform layer (also called preplate or marginal zone) distribute among layer I and layer VII (subplate). By means of bromodeoxyuridine labelling of cells becoming postmitotic, we have found evidence that, in the rat, an additional group of neurons of the primordial plexiform layer remains in the close vicinity of the ventricular zone. This finding, in line with the proposal by Marín‐Padilla (Z Anat. Entwicklungsgesch., 134, 117‐145, 1971), implies that the primordial plexiform layer suffers a tripartition after the formation of the cortical plate and of the intermediate zone (the latter soon becomes the embryonic white matter). Thus, primordial plexiform layer derivatives are in layer I, layer VII (subplate) and in the lower part of the embryonic white matter. This early generated neuronal population is also revealed with an antibody that recognizes the larger (67 kDa) isoform of glutamic acid decarboxylase (Kaufman et al., Science, 232, 1138‐1140, 1986). This is in accord with the earlier finding of a GABA‐containing cell population showing a similar spatiotemporal distribution. The early generated neurons of the embryonic white matter migrate tangentially and, in early postnatal animals, are found as interstitial cells in the medial regions of the subcortical white matter and at the midline in the corpus callosum. At caudal levels, similar cells invade the subpyramidal strata of the developing hippocampus. This tangential migration might explain the tangential dispersion of neural cell clones described in recent studies of cell lineage in the cerebral cortex.
Membrane Properties of Physiologically Classified Rat Dorsal Horn Neurons In Vitro: Correlation with Cutaneous Sensory Afferent Input
Authors: Lopez‐Garcia J. A. , King A. E.
Published: April 2006

Dorsal horn neurons in the young rat spinal cord‐hindlimb preparation were physiologically classified as wide dynamic range (WDR), nociceptive specific (NS) or low threshold (LT) according to their excitatory responses to low and high intensity mechanical stimuli applied to the hindlimb skin. Two additional types were classified: neurons displaying only sub‐threshold excitations (SUB) and neurons displaying inhibitory events (INH), such as inhibitory post‐synaptic potentials or interruption of spontaneous spiking following cutaneous stimulation. Direct intracellular current injection revealed four different patterns of spiking behaviour: group A neurons were characterized by tonic firing in response to depolarizing current pulses; group B neurons were strongly phasic, producing only one spike at the beginning of the pulse; group A‐B neurons generated an early unsustained (< 300 ms) burst of spikes; and group C neurons exhibited anomalous rectification in response to hyperpolarizing current which was followed by a voltage‐dependent rebound excitation. A statistically significant (P≤ 0.01) association existed between a neuron's physiological classification and its electrophysiological profile. The majority of WDR neurons responded with tonic firing and were assigned to group A, while NS neurons were strongly represented in group A‐B. All INH neurons were assigned to group C. LT neurons were distributed between groups A and A‐B, and SUB neurons were distributed between groups A and B. These data indicate, firstly, that dorsal horn neurons possess heterogeneous membrane properties and, secondly, that a relationship exists between a neuron's biophysical profile and its excitatory or inhibitory response to peripheral cutaneous afferent stimulation. The implications for dorsal horn somatosensory processing are discussed.
Membrane Arachidonic Acid Concentration Correlates with Age and Induction of Long‐term Potentiation in the Dentate Gyrus in the Rat
Authors: Lynch M. A. , Voss K. L.
Published: April 2006

We examined the induction and maintenance of long‐term potentiation (LTP) in vivo in the dentate gyrus of 4‐month‐old and 22‐month‐old urethane‐anaesthetized rats. High‐frequency stimulation of the perforant path induced an immediate increase in the slope of the population excitatory postsynaptic potential (EPSP), which was sustained in the 4‐month‐old animals for the duration of the experiment (45 min post‐tetanus). In the 22‐month‐old group, the mean slope of the population EPSP decreased almost to baseline by the end of the experiment. Examination of the individual records indicated that LTP was sustained for the duration of the experiment in half of the 22‐month‐old animals, while in the others only post‐tetanic potentiation was observed. Membrane arachidonic acid concentration was reduced in aged compared with young animals and was lowest in the subgroup of aged animals which failed to sustain LTP. Potassium‐stimulated, calcium‐dependent release of glutamate was also decreased in aged compared with young animals, but LTP was associated with an increase in glutamate release in the 4‐month‐old group and 22‐month‐old subgroup in which LTP was successfully sustained; no change was observed in the 22‐month‐old group in which LTP was not sustained. The results indicate a correlation between membrane arachidonic acid concentration, glutamate release and ability to sustain LTP in aged animals.
Axons Regenerate with Correct Specificity in Horizontal Slice Culture of the Postnatal Rat Entorhino‐hippocampal System
Authors: Li D. , Field P. M. , Yoshioka N. , Raisman G.
Published: April 2006

We have used slice culture of the entorhino‐hippocampal system to investigate (1) whether nerve fibres which are cut postnatally are able to regenerate and (2) whether the regenerating fibres are able to establish correct selective target specificity in the formation of their terminal fields. Slices of tissue were taken in the horizontal plane through the caudo‐ventral pole of the cerebral hemisphere of 9‐ to 10‐day‐old rats. Such slices maintain the entorhinal cortex in continuity with the hippocampus and intervening retrohippocampal areas. However, because of the dorsal inclination of the entorhino‐hippocampal projection fibres in situ, the segments of the entorhinal cortex and hippocampus contained within each individual horizontal slice were disconnected from each other. During subsequent culture, the formation of fibre connections between the entorhinal area and the hippocampal complex was studied by the extracellular and intracellular anterograde transport of biocytin or biotin dextran, the retrograde transport of biotin dextran or carbocyanine dyes, and by electrical stimulation and recording. For the first 24 h after taking the slice, there were no entorhinal projections beyond the deep white matter, and no fibres reached the hippocampus or dentate gyrus. After 3 days in culture a small number of growing fibres had perforated the subiculum and entered the target areas. Between 6 and 14 days these projections increased and matured. As in the normal adult brain, entorhinal layer II stellate cells projected correctly to the dentate gyrus and hippocampal field CA3, whereas layer III pyramidal cells projected to hippocampal field CA1 and the subiculum. The new fibres grew along both alvear and perforant pathways. Anterograde and retrograde labelling showed that the reciprocal projections from the pyramidal cells of the subiculum and CA1 to the entorhinal area had also been severed at the time of taking the slices, and had similarly regenerated. Our results demonstrate that by taking tissue slices in appropriate planes it is possible to study the regeneration of axons in the tissue environment through which they normally run. This approach avoids the use of coculture and the concomitant difficulties associated with the need for fibres to cross a coculture interface. In horizontal slices of postnatal tissue, severed fibre projections between the entorhinal cortex and the hippocampal complex can regenerate in both directions and re‐establish their correct laminar, pathway and target specificity.
Radioautographic Evidence that the GABAA Receptor Antagonist SR 95531 is a Substrate Inhibitor of MAO‐A in the Rat and Human Locus Coeruleus
Authors: Luque J. M. , Erat R. , Kettler R. , Cesura A. , Prada M. Da , Richards J. G.
Published: April 2006

The locus coeruleus (LC), a major noradrenergic nucleus in the brain, probably has a functional role in the regulation of anxiety states as well as vigilance, attention, learning and memory. LC neurons are under the inhibitory control of γ‐aminobutyric acid (GABA) via ionotropic GABAA receptors. However, to date, little is known of the receptor binding characteristics of these neurons. In the present investigation we therefore examined by receptor radioautography the localization of the binding sites for different components of the GABAA receptor complex in the rat and human LC. Both rat and human LC neurons have a high density of binding sites for the pyridazinyl‐GABA derivative [3H]SR 95531 (gabazine, a GABAA receptor antagonist for low affinity GABA recognition sites). However, at the concentrations used, no binding sites in the LC were detectable for the benzodiazepine receptor antagonist [3H]flumazenil, the GABAA receptor agonist (for high affinity sites) [3H]muscimol or the ionophore ligand [35S]t ‐butyl bicyclophosphorothionate (TBPS). Unexpectedly, the pharmacological specificity of [3H]SR 95531 binding to the LC differed markedly from that to most brain regions (IC50 values for GABA and RU 5135 respectively in the LC were > 10‐2 and 10‐3 M; and, for example, in the dentate gyrus the most labelled structure after the LC, 8 × 10‐7 and 1.8 × 10‐9 M). These differences prompted the further characterization of [3H]SR 95531 binding in the LC, revealing a significant affinity for monoamine oxidase type A (MAO‐A), which is highly concentrated in this nucleus. In a competition binding study, a reduction of up to 25% of the [3H]SR 95531 binding was observed with MAO‐A but not MAO‐B inhibitors, at concentrations which produce maximum but selective enzyme inhibition. Correspondingly, 2 h after the oral administration of supramaximal doses of the MAO‐A inhibitors moclobemide and Ro 41 ‐1049 (but not the MAO‐B inhibitor lazabemide) the in vitro binding of [3H]SR 95531 was markedly reduced (by 77 and 82% of controls respectively). Moreover, enzyme radioautography with [3H]Ro 41 ‐1049 revealed that SR 95531 has a significant affinity for MAO‐A (ICgo values were 10‐5 and 4x 10‐6 M in the LC and dentate gyrus respectively) but not for MAO‐B ([3H]lazabemide binding). Altogether, these findings suggest that the high‐affinity binding of [3H]SR 95531 to the LC mainly reflects its affinity for MAO‐A, which questions its utility as a selective ligand for low‐affinity GABA recognition sites in the CNS. It remains to be seen whether the dual pharmacological profile of SR 95531 (desinhibition of LC neurons and facilitation of noradrenergic transmission) can be exploited as a principle in the development of new anxiolytics or antidepressants.
MCPG Antagonizes Metabotropic Glutamate Receptors but not Long‐term Potentiation in the Hippocampus
Authors: Manzoni Olivier J. , Weisskopf Marc G. , Nicoll Roger A.
Published: April 2006

In the CA1 and CA3 regions of the guinea pig hippocampus, we have tested the ability of the new antagonist (RS)‐α‐methyl‐4‐carboxyphenylglycine (MCPG) to inhibit the well‐known effects of (trans)‐1‐amino‐cyclopentyl‐1,3‐dicarboxylate (ACPD), a specific agonist of glutamate metabotropic receptors. Whole‐cell recordings showed that MCPG was able to antagonize the blocking action of ACPD on IAHP in the CA1 region. In addition, we report here that MCPG also antagonized the presynaptic inhibitory actions of ACPD on field excitatory postsynaptic potentials in both areas CA1 and CA3. Thus, MCPG proved to be an effective tool for determining physiological roles of the glutamate metabotropic receptors in synaptic transmission in the hippocampus. We next tested the possible effects of this antagonist on long‐term potentiation (LTP). In completely blind experiments MCPG was without effect on LTP in both areas CA1 and CA3. In conclusion, our results suggest that, although MCPG is a valuable antagonist of the ACPD‐sensitive receptors, it has no inhibitory effect on LTP.
Influences of Horizontal Connections on Visual Responses in Rabbit Striate Cortex
Authors: Morin C. , Molotchnikoff S.
Published: April 2006

The goal of this study was to examine the role of horizontal connections in rabbit striate neurons. Anaesthetized rabbits were prepared in the usual fashion for single‐cell recordings in area 17 of the visual cortex. We compared responses evoked by moving and stationary stimuli prior to, during and after recovery from lateral microinjection of either lidocaine (n= 61), γ‐aminobutyric acid (GABA, n = 18) or bicuculline (n= 8) 2 mm from the recording site. This procedure allows evaluation of the contribution of neighbouring neurons in visual responses. Results showed that striate neurons are dependent on the adjacent cells1 excitability. Modification of responses to stationary targets suggests that lateral interactions play a role in the generation of discharges to fixed stimuli. Lateral inactivation preferentially influenced non‐directional over direction‐selective units. This influence usually resulted in the non‐directional neuron becoming directional by attenuation of the visually driven response in one direction. Simple and complex cells tended to be influenced differently by lateral inactivation. Simple cells became less responsive, whereas complex cells became more responsive. This dichotomy among cellular types suggests that simple cells receive mainly excitatory horizontal influences, while complex cells are contacted mostly by lateral inhibitory inputs.
The Effect of Corticosterone on Reactivity to Spatial Novelty is Mediated by Central Mineralocorticosteroid Receptors
Authors: Oitzl Melly S. , Fluttert Marc , Ron de Kloet E.
Published: April 2006

Corticosterone, secreted by the adrenal glands, binds to central mineralocorticoid receptors with high affinity and to glucocorticoid receptors with a tenfold lower affinity. In previous studies we have shown that the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effects. In this study we examined in particular the mineralocorticoid receptor‐mediated effect of corticosterone on the control of the behavioural response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal‐intact rats the presence of an object in the centre of an open field alters the time spent and distance walked in the centre compared to the peripheral area, i.e. the pattern of reactive locomotor activity is changed. Using this paradigm we found that 1 day after removal of the adrenals the rats increased their behavioural reactivity towards the object. Treatment of adrenalectomized rats with a low dose of corticosterone (50 μg/kg s.c.) 1 h prior to testing restored the behavioural reactivity to the level of sham‐operated, intact rats. Surprisingly, a high dose of corticosterone (1000 μg/kg s.c.) also increased the rat's reactivity towards the object. The same high dose of corticosterone given to adrenal‐intact rats also increased behavioural reactivity. Pretreatment of these rats with an intracerebroventricular injection of the selective mineralocorticoid receptor antagonist RU28318 (100 ng/μl) prevented the corticosterone‐induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/μl) was not effective. Administration of the mineralocorticoid receptor antagonist without corticosterone to adrenal‐intact rats also increased behavioural reactivity, but this increase did not reach statistical significance. General locomotor activity was not affected by either treatment. In conclusion, we found a U‐shaped relationship between the pattern of behavioural reactivity in a novel environment and the circulating plasma corticosterone level. The response to spatial novelty appeared to be sensitive with respect to the activation and blockade of central, presumably hippocampal mineralocorticoid receptors.
Rectification Properties and Ca2+ Permeability of Glutamate Receptor Channels in Hippocampal Cells
Authors: Lerma J. , Morales M. , Ibarz J. M. , Somohano F.
Published: April 2006

Excitatory amino acids exert a depolarizing action on central nervous system cells through an increase in cationic conductances. Non‐NMDA receptors have been considered to be selectively permeable to Na+ and K+, while Ca2+ influx has been thought to occur through the NMDA receptor subtype. Recently, however, the expression of cloned non‐NMDA receptor subunits has shown that α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors are permeable to Ca2+ whenever the receptor lacks a particular subunit (edited GluR‐B). The behaviour of recombinant glutamate receptor channels predicts that Ca2+ would only permeate through receptors that show strong inward rectification and vice versa, i.e. AMPA receptors with linear current‐voltage relationships would be impermeable to Ca2+ . Using the whole‐cell configuration of the patch‐clamp technique, we have studied the Ca2+ permeability and the rectifying properties of AMPA receptors, when activated by kainate, in hippocampal neurons kept in culture or acutely dissociated from differentiated hippocampus. Cells were classified according to whether they showed outward rectifying (type I), inward rectifying (type II) or almost linear (type III) current‐voltage relationships for kainate‐activated responses. AMPA receptors of type I cells (52.2%) were mostly Ca2+‐impermeable (PcaIPcs= 0.1) while type II cells (6.5%) expressed Ca2+‐permeable receptors (PcaIPcs=0.9).Type III cells (41.3%) showed responses with low but not negligible Ca2+ permeability (PcaIPcs= 0.18). The degree of Ca2+ permeability and inward rectification were well correlated in cultured cells, i.e. more inward rectification corresponded to higher Ca2+ permeability. In acutely dissociated neurons, the restricted activation of the receptors located either in dendritic or somatic membranes revealed that inward rectifying (i.e. Ca2+‐permeable) AMPA receptors are preferentially located in the dendritic shaft (i.e. synaptic field). Our results indicate that oligomeric AMPA receptors of different subunit composition are coexpressed in dissimilar proportions in different cells, which would explain the incomplete inward rectification and graded Ca2+ permeability. In addition, Ca2+‐permeable AMPA receptors may exhibit non‐homogeneous subcellular distribution.
GABA‐activated Chloride Currents of Postnatal Mouse Retinal Ganglion Cells are Blocked by Acetylcholine and Acetylcarnitine: How Specific are Ion Channels in Immature Neurons?
Authors: Bähring R. , Standhardt H. , Martelli E. Arrigoni , Grantyn R.
Published: April 2006

The goal of this study was to clarify pharmacological properties of GABAA receptors in cells of the mouse retinal ganglion cell layer in situ. Spontaneous synaptic currents and responses to exogenous GABA were recorded from individual neurons in retinal whole mounts (postnatal days 1–3) or retinal stripe preparations (postnatal days 4–6). Drugs were applied by a fast local superfusion system. Current responses were measured with the patch‐clamp technique in the whole‐cell configuration. All cells responded to exogenous GABA (average EC50 and Hill coefficient: 16.7 μM and 0.95 respectively) and generated GABAergic synaptic currents in response to elevated KCI. GABA‐induced currents of retinal ganglion cells were blocked by bicuculline, picrotoxin and Zn2+, as well as strychnine, and increased by pentobarbital, clonazepam and 3α‐hydroxy‐5α‐pregnan‐20‐one. In some retinal ganglion cells GABA caused an increase in the frequency of spontaneous synaptic currents, which points to a partially depolarizing action of this traditionally inhibitory neurotransmitter in the neural retina. Our major observation is that acetylcholine and acetylcarnitine blocked or reduced GABAergic inhibitory postsynaptic currents and responses to exogenous GABA. This effect was seen in only a fraction of retinal ganglion cells and occurred in both the undesensitized and the desensitized state of the GABAA receptor. The block was voltage‐independent and persisted during coapplication with the nicotinic and muscarinic acetylcholine receptor antagonists D‐tubocurarine and atropine. In contrast to GABA‐activated Cl− currents, glycine‐activated Ch currents remained unaffected by acetylcholine and acetylcarnitine. Acetylcarnitine had no effect on voltage‐activated Ca2+ channel currents and glutamate‐activated currents. Similar results were obtained in a dissociated cell culture preparation from the neonatal rat superior colliculus. In these cells acetylcholine induced a rightward shift in the dose ‐ response curve for GABA. Taken together, these results indicate that acetylcholine and acetylcarnitine can act directly at the GABAA binding site and thereby reduce the action of GABA in the immature retina.
Shaker Mutants Lack Post‐tetanic Potentiation at Motor End‐plates
Authors: Delgado Ricardo , Latorre Ramon , Labarca Pedro
Published: April 2006

The two‐electrode voltage clamp technique was employed to measure end‐plate currents in larval neuromuscular junctions of wild‐type (Canton‐S) and of three different Drosophila Shaker mutants: ShakerKS133, Shaker102 and f5Shaker5. In the Shaker mutants, nerve‐evoked end‐plate currents (neepc) were 4–5‐fold larger than those measured in Canton‐S. Shaker motor end‐plates were found to lack post‐tetanic potentiation (PTP), but could undergo facilitation. Moreover, PTP but not facilitation was lost in wild‐type larvae if the neuromuscular junction was exposed to 4‐aminopyridine (4‐AP), a blocker of Shaker A‐type K+ currents. End‐plate currents were depressed by Ca2+ channel blockers like Mg2+, at millimolar concentrations, and Co2+ and Cd2+, at micromolar concentrations, but not by nifedipine (100 nM) and verapamil (100 nM). After exposure to Ca2+ channel blockers, Shaker end‐plates exhibited PTP. In particular, Cd2+ was most effective in depressing neepes and in restoring PTP in all Shaker mutants. The results obtained indicate the abnormal function of Shaker K+ channels at motor nerves specifically abolishes PTP in Drosophila larval neuromuscular junctions.
Inverted Pyramidal Neurons and Interneurons in Cat Cortical Subplate Zone are Labelled by Monoclonal Antibody SP1
Authors: Wahle Petra , Lübke Joachim , Naegele Janice R.
Published: April 2006

During development, the subplate zone of the cat neocortex contains neuronal populations with distinct morphological and neurochemical phenotypes. A subset of those are specifically recognized by a mouse monoclonal antibody termed SUBPLATE‐1 (SP1), which was generated against tissue homogenates of kitten cortical white matter. SP1 stains cell bodies and proximal dendrites, but rarely distal dendrites, axonal arbors or spines. In order to characterize morphologically the SP1 imunoreactive subplate cell types, we combined SP1 immunohistochemistry with intracellular iontophoretic injections of Lucifer yellow. The majority of double‐labelled neurons were inverted pyramids with a single thicker spine‐covered dendrite that descended into the white matter and a tuft of thinner spinous dendrites that ascended from the upper somatic pole, but generally remained confined to the white matter. Other double‐labelled neurons were multipolar to bitufted, although often equipped with one thicker descending dendrite. In inverted pyramidal cells, the axons originated from the descending dendrite or, more rarely, from the lower portion of the soma, and descended into the white matter. They formed collaterals recurring toward the grey matter. The presence of dendritic spines on double‐labelled pyramidal cells and the axonal arborization patterns were two novel features not revealed previously by SP1 immunohistochemistry alone. The inverted pyramidal morphology was typical for double‐labelled neurons located in the subplate szone below the apices of the gyri, whereas those located below the flanks or sulci or deep in the white matter soften displayed a bitufted or multipolar spinous morphology. A minority of the double‐labelled neurons were multipolar with smooth dendrites and locally branching axons. These results suggest that in the cat subplate zone, a majority of the cells expressing the SP1 antigen are spinous, and we termed the spinous subplate cells ‘subplate pyramidal neurons’.
Requirement of Metabotropic Glutamate Receptors for the Generation of Inflammation‐evoked Hyperexcitability in Rat Spinal Cord Neurons
Authors: Neugebauer Volker , Lücke Thomas , Schaible Hans‐Georg
Published: April 2006

In the central nervous system the transmitter L‐glutamate activates both ionotropic receptors coupled to cation channels and metabotropic receptors coupled to G‐proteins. The role of metabotropic receptors in the processing of mechanosensory and nociceptive information was studied in a subset of spinal cord neurons with afferent input from the knee joint in anaesthetized rats using electrophysiological methods. The ionophoretic administration of L‐2‐amino‐3‐phosphonopropionic acid (L‐AP3), an antagonist at the metabotropic receptor, had no effect on the responses to innocuous and noxious pressure applied to the normal knee joint, although the antagonist prevented the potentiation of these responses evoked by the ionophoretic administration of a specific agonist at the metabotropic receptor, trans‐(±)‐1‐amino‐(1S,3R)‐cyclopentane‐dicarboxylic acid (t‐ACPD). By contrast, in neurons that were rendered hyperexcitable by acute inflammation in the knee joint L‐AP3 reduced the responses to pressure applied to the knee. When L‐AP3 was applied during induction of inflammation and throughout the subsequent 1.5 h the spinal neurons did not develop hyperexcitability over this time period. L‐AP3 did not impair the activation of ionotropic N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors by the specific agonists. We conclude that spinal metabotropic glutamate receptors are not involved in the mediation of responses to innocuous and noxious mechanical stimuli applied under normal conditions. They are required, however, for the generation of inflammation‐evoked hyperexcitability of spinal cord neurons, a form of functional plasticity underlying the painfulness in pathophysiological conditions such as inflammation.
The Length – Response Properties of Cells in the Feline Perigeniculate Nucleus
Authors: Jones H. E. , Sillito A. M.
Published: April 2006

Perigeniculate cells receive visual input from the dorsal lateral geniculate nucleus (dLGN) and from the visual cortex. In contrast to the extensive literature documenting dLGN and cortical cell responses, comparatively little quantitative data exists for perigeniculate nucleus cells, and very little is known about the role of the corticofugal input to the perigeniculate nucleus. We have previously shown that dLGN relay cells have sharply length‐tuned receptive fields and that a significant component of this is dependent on the corticofugal system. In this report, we have explored the length – response properties of perigeniculate nucleus cells in the presence and absence of corticofugal feedback. The response profiles of most perigeniculate nucleus cells contrasted markedly with the sharply length‐tuned fields of dLGN cells, but exhibited a notable resemblance to those exhibited by VI cells with short summation lengths, which have recently been shown to constitute a considerable proportion of the layer VI cell population. This might suggest that the responses of perigeniculate nucleus cells to long bars derive from their cortical input. However, our data failed to reveal a discernible change in their profiles after removal of the corticofugal drive. This surprising observation implies that their length‐tuning profiles follow from subcortical circuitry. The ways in which this might occur are discussed.
Anatomical and Electrophysiological Evidence for an Excitatory Amino Acid Pathway from the Thalamic Mediodorsal Nucleus to the Prefrontal Cortex in the Rat
Authors: Pirot Sylvain , Jay Thérèse M. , Glowinski Jacques , Thierry Anne‐Marie
Published: April 2006

This study was undertaken to identify the neurotransmitter of the projection from the thalamic mediodorsal nucleus (MD) to the prefrontal cortex (PFC) using both retrograde transport of D‐[3H]aspartate and electrophysiological approaches in the rat. Unilateral microinjections of D‐[3H]aspartate performed into the prelimbic area of the PFC resulted in dense labelling of numerous cells in the ipsilateral MD. Excitatory responses were observed in PFC neurons after electrical stimulation of the MD. However, since cortical neurons project to the MD, these excitatory responses could have resulted either from the activation of the MD‐PFC pathway and/or from the activation of recurrent collaterals of antidromically driven cortico‐thalamic fibres. The conduction time of each of these two reciprocal pathways was determined by antidromic activation. Short latency excitatory responses resulted from activation of the MD‐PFC pathway. They were predominantly observed in PFC neurons located in layer III and evoked at low frequency stimulation (0.3–1 Hz). These excitatory responses disappeared or were replaced by longer latency responses when higher frequency stimulations (3–10 Hz) were used. MD‐evoked responses were blocked by the iontophoretic application of the AMPA receptor antagonist CNQX into the PFC. These results indicate that the MD‐PFC pathway utilizes glutamate and/or aspartate as the neurotransmitter and that its activation induces excitation in PFC neurons through AMPA receptors. Even though the local application of the NMDA receptor antagonist APV was ineffective, a contribution of these receptors in MD‐PFC transmission cannot be excluded.
Interhemispheric Structural Asymmetry Induced by a Lateralized Reaching Task in the Rat Motor Cortex
Authors: Díaz Eugenia , Pinto‐Hamuy Teresa , Fernández Víctor
Published: April 2006

The effects of a lateralized reaching task on the morphological structure of the rat motor cortex were studied during the early postweaning period. Our results show that the consistent use of one forelimb accounts for a significant decrease in the numerical density of cells and an increase in cortical thickness of the contralateral‘forelimb’motor cortex. As a consequence of the early motor training the cell distribution, which is lower rostrally than caudally in nontrained hemispheres, is reversed in the trained hemispheres. This may be interpreted as the specific motor training triggering a higher neuronal branching in the corresponding cortical region. The present findings may further the understanding of the mechanisms involved in the generation of morphological brain asymmetries.