bluuebunny/crossref_metadata_2025 huggingface dataset:
Septotemporal variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats
Authors: Cavazos José E. , Golarai Golijeh , Sutula Thomas P.
Published: May 2005

Previous studies have demonstrated regional variation in the anatomical organization and physiological properties of the hippocampus along its septotemporal (dorsoventral) axis. In this study, regional variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats was characterized with a scoring method for assessment of the distribution of mossy fiber synaptic terminals detected by Timm histochemistry. In normal rats, there was a sparse projection of the mossy fiber pathway into the supragranular region near the tips and crest of the dentate gyrus along the entire septotemporal axis, and a prominent projection into the supragranular region at the temporal pole. Kindling of the perforant path, amygdala, and olfactory bulb induced synaptic reorganization of the mossy fiber pathway into the supragranular region along the entire septotemporal axis of the dentate gyrus. There was regional variation of the seizure‐induced synaptic reorganization along this axis, and distinct septotemporal patterns were observed as a function of the site of kindling stimulation. Kindling of the perforant path induced mossy fiber synaptic reorganization that was relatively more prominent in the septal pole than in the temporal pole of the dentate gyrus. In contrast, rats that received kindling stimulation of the amygdala had a more uniform distribution of synaptic reorganization along the septotemporal axis. As there is regional variation of the anatomical and physiological properties of the human epileptic hippocampus, these observations could be pertinent to human epilepsy.
Quantal and subquantal GABAergic transmissions in cultured rat hippocampal neurons
Authors: Vautrin Jean , Schaffner Anne E. , Barker Jeffery L.
Published: May 2005

At the neuromuscular junction, spontaneous miniature excitatory synaptic currents mediated by acetylcholine are considered elementary, “quantal” transmissions. These miniature conductances can be quantitatively dichotomized into a large‐mode class whose mode is the mean of a normal, bell‐shaped distribution and a small‐mode class whose distribution is skewed to lower values with its mode being a fraction of the large‐mode class. The large‐mode class constitutes the population of synaptic signals originally utilized to formulate tenets of “quantal” transmission, which have been tacitly adopted in more recent studies of fast transmission at central synapses. Large‐ and small‐mode conductance classes of inhibitory synaptic elementary conductances mediated by GABA have now been recorded in cultured hippocampal neurons (Vautrin J, Schaffner AE, Barker JL, 1991, Neurosci Lett 138:67). Pairs of hippocampal neurons were patch recorded at optimal signal‐to‐noise and, using time course analysis, two elementary fluctuations (0.1–0.3 nS and 1–2 nS) were found within synaptic conductances evoked either by presynaptic action potentials or by presynaptic terminal stimulation. These results were interpreted with a simple model that shows how different frequencies of unitary GABA release can generate either small‐mode, skew‐distributed conductance (0.5–3 kHz) or large‐mode, normally‐distributed conductances (≥ 10 kHz). Only the latter satisfies the original tenets of the classic quantal theory.
Epilepsy induced collateral sprouting of hippocampal mossy fibers: Does it induce the development of ectopic synapses with granule cell dendrites?
Authors: Represa Alfonso , Jorquera Isabel , le gal la Salle Gildas , Ben‐Ari Yehezkel
Published: May 2005

In the present study, using Golgi and electron microscopy techniques, experimentally induced epilepsy (kindling and kainate treatment) elicited collateral sprouting of mossy fibers in rat hippocampus. Collateral branches invade the hilus, cross the granule cell layer, and distribute throughout the inner third of the molecular layer. These newly developed collaterals may acquire the typical features of mossy fibers including giant fiber varicosities (mousses), although the mean surface of these mousses was thinner in these collaterals than in terminal branches. Granule cell dendrites may develop giant thorny excrescences, suggesting that the targets of these collaterals are granule cells. Giant synaptic boutons appear in the inner third of molecular layer of epileptic rats. These boutons acquire the morphological features of mossy fiber boutons and made multiple synaptic contacts with dendritic spines. The analysis of the profile types suggests that some of the newly developed collateral mossy fibers made hypotrophic synaptic contacts.
Hyperpolarizing synaptic potentials evoked in CA1 pyramidal cells by glutamate stimulation of interneurons from the oriens/alveus border of rat hippocampal slices. II. sensitivity to GABA antagonists
Authors: Samulack Donald D. , Lacaille Jean‐Claude
Published: May 2005

The receptor type mediating the inhibitory postsynaptic potentials (glut‐IPSPs), recorded in CA1 pyramidal cells, as a result of glutamate stimulation of interneurons in stratum oriens near the alveus (O/A) was assessed and compared to the type mediating recurrent IPSPs evoked by recurrent activation of interneurons through glutamate stimulation of pyramidal cells in stratum pyramidale (PYR). In response to repetitive electrical stimulation, the peak amplitude of both the O/A glut‐IPSP and the PYR glut‐IPSP was attenuated (n = 5) in parallel to the reduction in amplitude of the early and late components of the electrically evoked response (stimulus‐evoked disinhibition). This suggested the involvement of GABAergic receptors and attested that the interneurons activated during glut‐IPSPs were also involved in the circuitry of the electrically evoked IPSPs. The local application of the selective GABAA antagonist bicuculline (100–200 μM) to the slice resulted in a significant reduction in the amplitude of both the O/A (by 76.5%; n = 9) and PYR (by 86.2%; n = 5) glut‐IPSPs, in parallel to a decrease of the electrically evoked early IPSP, but not of the late IPSP. The presence of the GABAB antagonist 2‐hydroxy‐saclofen (1 mM) was able to significantly reduce the amplitude of the O/A glut‐IPSPs (by 27.5%; n = 7) and of the electrically evoked late IPSP, but not the PYR glut‐IPSP (n = 3). Although the application of phaclofen (20 mM) to the slice reduced the amplitude of the O/A glut‐IPSPs (n = 3), the reduction was not statistically significant. These results suggest that recurrent IPSPs elicited from activation of interneurons by stimulation of pyramidal cells are mediated solely via GABAA receptors. Inhibitory postsynaptic potentials elicited from stimulation of interneurons in O/A were also mediated mostly by GABAA receptors, but in addition, displayed a minor component mediated by GABAB receptors. Therefore, since a large proportion of interneurons in O/A are recurrently excited by pyramidal cells (Lacaille J‐C et al., 1987, J Neurosci 7:1979–1993), and since recurrent IPSPs appeared mediated by GABAA receptors, a subpopulation of interneurons activated from O/A might exist that do not receive recurrent excitation but can inhibit pyramidal cells via GABAB receptors.
Maps, routes, and the hippocampus: A neural network approach
Authors: Schmajuk Nestor A. , Thieme Aaron D. , Blair Hugh T.
Published: May 2005

This study describes hippocampal participation in maze navigation in terms of a real‐time, biologically plausible neural network. The system is composed of (1) a goal‐seeking mechanism, (2) a cognitive map system, and (3) a route system. The goal‐seeking mechanism displays exploratory behavior until either the goal is found or a sufficiently strong prediction of the goal is generated. The cognitive map is a topological map that stores associations between places and views of accessible places, and between places and reward. The route system establishes associations between cues and reward. Both systems compete with each other to establish associations with the reward, with the cognitive system generally overshadowing the route system. In agreement with previous models, it is assumed that the hippocampus modulates the storage of cognitive maps in cortical areas and mediates the competition between cognitive maps and route systems. In agreement with previous models, it is assumed that the hippocampus modulates the storage of cognitive maps in cortical areas and mediates the competition between cognitive maps and route systems. After hippocampal lesions, animals navigate through mazes making use of the route system. Computer simulations show that the network effectively describes latent learning, detour behavior, and place learning in normal and hippocampal‐and cortical‐lesioned animals.
Projection of the entorhinal layer II neurons in the rat as revealed by intracellular pressure‐injection of neurobiotin
Authors: Tamamaki Nobuaki , Nojyo Yoshiaki
Published: May 2005

A component of the perforant path, projection of the entorhinal layer II neurons, was investigated by recovering intracellularly labeled layer II neurons from the medial or intermediate entorhinal cortex in rats. The labeled layer II spiny stellate neurons had axon collaterals in layers I, II, and III of the entorhinal cortex as well as some axon collaterals in the subiculum. The stem axons gave rise to terminal axon branches that covered the entire extent (suprapyramidal blade, crest, and infrapyramidal blade) of the dentate gyrus and the CA2–3 fields in the transverse plane, forming a sheet‐like formation. The axon arbor in the hippocampal formation spread up to 2 mm wide in a septotemporal direction. The sheet‐like formation of the axon arbors was a narrow layer in the suprapyramidal blade and in the stratum lacunosum‐moleculare of the CA2–3 fields. The layer became wider in the crest and infrapyramidal blade of the dentate gyrus. This study shows that the entorhinohippocampal circuit is not a simple circle from single cells level.
Hippocampal mediation of stimulus representation: A computational theory
Authors: Gluck Mark A. , Myers Catherine E.
Published: May 2005

The authors propose a computational theory of the hippocampal region's function in mediating stimulus representations. The theory assumes that the hippocampal region develops new stimulus representations that enhance the discriminability of differentially predictive cues while compressing the representation of redundant cues. Other brain regions, including cerebral and cerebellar cortices, are presumed to use these hippocampal representations to recode their own stimulus representations. In the absence of an intact hippocmpal region, the theory implies that other brain regions will attempt to learn associations using previously established fixed representations. Instantiated as a connectionist network model, the theory provides a simple and unified interpretation of the functional role of the hippocampal region in a wide range of conditioning paradigms, including stimulus discrimination, reversal learning, stimulus generalization, latent inhibition, sensory preconditioning, and contextual sensitivity. The theory makes novel predictions regarding the effects of hippocampal lesions on easy‐hard transfer and compound preexposure. Several prior qualitative characterizations of hippocampal function–including stimulus selection, chunking, cue configuration, and cotextual coding–are identified as task‐specific special cases derivable from this more general theory. The theory suggests that a profitable direction for future empirical and theoretical research will be the study of learning tasks in which both intact and lesioned animals exhibit similar initial learning behaviors but differ on subsequent transfer and generalization tasks.
Flip side of synaptic plasticity: Long‐term depression mechanisms in the hippocampus
Authors: Christie Brian R. , Kerr D. Steven , Abraham Wickliffe C.
Published: May 2005

There is growing interest in the phenomenon of long‐term depression (LTD) of synaptic efficacy that, together with long‐term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca2+ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley‐Liss, Inc.
Dissociation between long‐term potentiation and associated changes in field epsp waveform in the hippocampal CA1 region: An in vitro study in guinea pig brain slices
Authors: Asztely F. , Gustafsson B.
Published: May 2005

The present study examines changes in field excitatory postsynaptic potential (EPSP) waveform in association with long‐term potentiation (LTP) in the CA1 region of the hippocampal slice preparation. Experiments were performed in the presence of the GABAA‐antagonist picrotoxin. With test field EPSP about one‐third the size of that evoking spike activity (measured in the cell body layer along the same somatodendritic axis as the dendritic recording) a decreased decay time constant (approximately 8%) was seen in association with LTP. This change in field EPSP waveform was not associated with any apparent spike activity in the cell body recording. Nevertheless, several findings suggest that increased spike activity explains the change in the decay time constant of the field EPSP during LTP. First, when reducing the stimulation strength after the induction of LTP to obtain a field EPSP of the same magnitude as the pretetanus one, the change of the decay time constant was reduced to only 2.8%. Second, when using small test field EPSP (about one‐fourth the size of that evoking spike activity) the decay time constant was not significantly affected in association with LTP. Third, when cutting the slice in such a manner that spike activity originating from somatic regions closer to the stimulating electrode was removed, the EPSPs decay time constant was not significantly affected in association with LTP. It is concluded that LTP is not associated with a change in the shape of the field EPSP. © 1994 Wiley‐Liss, Inc.
Somatostatin‐immunoreactivity in the hippocampus of mouse, rat, guinea pig, and rabbit
Authors: Buckmaster Paul S. , Kunkel Dennis D. , Robbins Richard J. , Schwartzkroin Philip A.
Published: May 2005

The hippocampi of species commonly used for in vitro physiologic studies were examined to determine if there were species‐specific and regional differences in somatostatin immunoreactivity. The distributions of somatostatin‐immunoreactive somata and fiber plexuses were determined, and the concentration of somatostatin along the septotemporal axis of the hippocampus was measured using a radioimmunoassay. There are many similarities in the patterns of somatostatin immunoreactivity in the hippocampi of mice, rats, guinea pigs, and rabbits. All species had a relatively even distribution of somatostatin‐positive perikarya across three fields of the hippocampus (dentate gyrus, CA3, and CA1‐2), a similar distribution of somatostatin‐immunoreactive perikarya across the strata of the CA1‐2 field and the dentate gyrus; and more somatostatin‐positive cells in temporal than in septal hippocampus. However, there are species‐specific differences in the distribution of somatostatin‐immunoreactive perikarya across the strata of CA3. In addition, unlike the other species examined, mice appeared not to have a somatostatin‐immunoreactive fiber plexus in the molecular layer of the dentate gyrus. The functional significance of these differences remains to be determined. © 1994 Wiley‐Liss, Inc.
Glutamatergic hippocampal formation projections to prefrontal cortex in the rat are regulated by GABAergic inhibition and show convergence with glutamatergic projections from the limbic thalamus
Authors: Gigg John , Tan Aiko M. , Finch David M.
Published: May 2005

Anatomic and physiologic studies in the rat have shown projections from the hippocampal formation (HF) and mediodorsal (MD) thalamic nucleus to the medial prefrontal cortex (mPFC). The authors used multi‐barrel iontophoresis to: confirm the neurotransmitter used in the projection from HF to mPFC; investigate the role of GABAergic inhibition in the regulation of this projection; and examine the functional convergence of projections from HF and MD onto single mPFC neurons. During HF stimulation, nine cells (6%) showed excitation followed by prolonged inhibition, 39 cells (26%) showed prolonged inhibition alone and 100 cells (68%) showed no clear response. In a further 12 cells that showed no predrug excitation to HF stimulation (representing 16% of the cells in this category), iontophoresis of the GABAA antagonist bicuculline methiodide (BMI) revealed excitatory responses. A total of six mPFC cells (38% of the cells showing excitatory responses to HF stimulation) showed convergent excitation to HF and MD thalamic (or adjacent paratenial nucleus) stimulation. Five out of eight (63%) of the predrug or BMI‐revealed excitatory responses of mPFC neurons to HF stimulation were selectively decreased after AMPA antagonist iontophoresis (either CNQX or DNQX). These data confirm that the HF projection to prefrontal cortex is, at least in part, glutamatergic; suggest that the responses of mPFC neurons to activity in this HF pathway are regulated by GABAergic inhibition; and indicate that projections from HF and MD converge onto single mPFC neurons. © 1994 Wiley‐Liss, Inc.
Hippocampal sympathetic ingrowth and cholinergic denervation alter hippocampal muscarinic cholinergic receptors
Authors: Harrell Lindy E. , Ayyagari Viswaprabhu , Peagler Andrea , Parsons Dee S.
Published: May 2005

Cholinergic denervation of the hippocampus by medial septal (MS) lesions results in the ingrowth of peripheral sympathetic fibers, originating from the superior cervical ganglia, into the hippocampus. To determine the effect of hippocampal sympathetic ingrowth (HSI) [3H]‐QNB (L‐quinuclidinyl [benzilic‐4, 4(n)] benzilate) binding was assessed in the dorsal and ventral hippocampus four weeks after MS lesions. In dorsal hippocampus, HSI was found to signignificantly increase the number (Bmax) of [3H]‐QNB binding sites and to normalize the decrease in affinity found in animals with MS lesions plus ganglionectomy (i. e., no ingrowth). In ventral hippocampus, HSI was found to normalize the increased number of binding sites and decreased affinity found in animals with MS lesions without ingrowth. No effect on either Kd or Bmax was found in animals that had undergone ganglionectomy with sham MS lesions. These results suggest that HSI can induce changes in hippocampal muscarinic cholinergic receptors. © 1994 Wiley‐Liss, Inc.
Alterations of inhibitory synaptic responses in the dentate gyrus of temporal lobe epileptic patients
Authors: Uruno Katsuhisa , O'Connor Michael J. , Masukawa Leona M.
Published: May 2005

The number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as “more excitable” (multiple population spikes) or “less excitable” (a single population spike). During orthodromic stimulation, “more excitable” tissue exhibited less paired‐pulse depression in comparison to “less excitable” tissue. During antidromic stimulaltion, both multiple population spikes and paired‐pulse depression were observed in “more excitable” tissue. “Less excitable” tissue exhibited a single antidromic spike and often on antidromically evoked paired‐pulse depression. The strength of antidromic paired‐pulse depression was correlated positively with the number of antidromic spikes and was correlated negatively with orthodromic paired‐pulse depression. Although orthodromic and antidromic paired‐pulse depression were correlated to the number of orthodromically evoked populaltion spikes, this correlation was not as strong as that between orthodromic paired‐pulse depression, antidromic paired‐pulse depression, and number of antidromically evoked population spikes.

The antidromic paired‐pulse depression observed in tissue exhibiting antidromically evoked multiple population spikes was enhanced rather than blocked by bicuculline. In addition, the blockade of the antidromic paired‐pulse depression by CNQX indicated that this inhibition is mediated by an AMPA‐type glutamatergic synapse. We suggest that alterations in circuitry occur in the dentate gyrus of some temporal lobe epileptic patients and were manifested by both a loss of inhibitory input as well as an increase of inhibition, which was dependent on the pathway of stimulaltion. The results of pairing antidromic and orthodromic stimuli were consistent with these conclusions. © 1994 Wiley‐Liss, Inc.
Multideterminant role of calcium in hippocampal synaptic plasticity
Authors: Teyler Timothy J. , Cavus I. , Coussens C. , Discenna P. , Grover L. , Lee Y. P. , Little Z.
Published: May 2005

Hippocampal CA1 cells possess several varieties of long‐lasting synaptic plasticity: two different forms of long‐term potentiation (LTP) and at least one form of long‐term depression (LTD). All forms of synaptic plasticity are induced by afferent activation, all involve Ca2+ influx, all can be blocked by Ca2+ chelators, and all activate Ca2+‐dependent mechanisms. The question arises as how different physiological responses can be initiated by activation of the same second messenger. We consider two hypotheses which could account for these phenomena: voltage‐dependent differences in cytosolic Ca2+ concentration acting upon Ca2+ substrates of differing Ca2+ affinities and compartmentalization of the Ca2+ and its substrates. © 1994 Wiley‐Liss, Inc.
Spontaneous and synaptic input from granule cells and the perforant path to dentate basket cells in the rat hippocampus
Authors: Kneisler Tracy B. , Dingledine Raymond
Published: May 2005

To characterize excitatory inputs to dentate basket cells from dentate granule cells and the perforant path, the whole‐cell recording technique was used in neonatal rat hippocampal slices. Spontaneous excitatory input to basket cells was also examined and compared to that of other interneurons in the dentate gyrus. Basket cells were separable from other neurons in the dentate gyrus based on morphology and location, as determined by biocytin staining following recording, and by resting membrane potential, propensity to fire action potentials spontaneously, and miniature excitatory postsynaptic current (EPSC) characteristics. Minimal electrical stimulation of the granule cell layer evoked in basket cells short latency EPSCs that were composed of both N‐methyl‐D‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate (AMPA) components as judged by their time course, voltage dependence, and blockade by selective antagonists. Perforant path EPSCs exhibited slower kinetics than EPSCs evoked by granule cell stimulation. Like granule cell evoked EPSCs, however, perforant path EPSCs were composed of both NMDA and AMPA components. Minimal electrical stimulation of the granule cell layer and perforant path evoked monosynaptic EPSCs in only 67% and 62% of the trials, respectively, suggesting that these inputs are as unreliable as previously determined inputs from CA3 pyramidal cells (48%).

Tetrodotoxin‐insensitive spontaneous miniature EPSCs were frequent in basket cells and non‐basket interneurons residing either at the border between the granule cell layer and the hilus or deep within the hilus. Miniature EPSCs recorded from all cells held at −70 mV were blocked completely by 3 μSM 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX). Though a component of the miniature EPSCs recorded from border and deep hilar interneurons at +40 mV was blocked by the NMDA receptor antagonist D‐2‐amino‐phosphonovaleric acid (D‐APV), miniature EPSCs in basket cells were insensitive to D‐APV.

We conclude that input from granule cells and the perforant path results in activation of basket cells via glutamatergic synapses that employ both NMDA and AMPA receptors. These inputs to basket cells likely contribute to feedback and feedforward inhibition of granule cells. The absence of an NMDA receptor component in spontaneous miniature EPSCs of dentate basket cells implies a difference in organization of excitatory synapses made onto basket cells compared with other hilar interneurons. © 1995 Wiley‐Liss, Inc.
Changes in exploratory activity following stimulation of hippocampal 5‐HT1A and 5‐HT1B receptors in the rat
Authors: Buhot Marie‐Christine , Naili Said
Published: May 2005

The object exploration task allows the measure of changes in locomotor and exploratory activities, habituation, and reaction to a spatial change and to novelty. The effects of intrahippocampal (dorsal CA1 field) microinjections of serotonin 1 receptor (5‐HT1) agonists on these behavioral components were evaluated in the rat. 8‐Hydroxy‐2‐(din‐propylamino)‐tetralin (8‐OH‐DPAT,5 μg/μl) was used as a 5‐HT1A agonist, 3‐(1,2,5,6‐tetrahydropyrid‐4‐yl) pyrrolo[3,2‐b] pyrid‐5‐one (CP 93,129, 16 μg/μl) as a 5‐HT1B agonist, and scopolamine (10 μg/μl) as a muscarinic cholinergic antagonist. Scopolamine induced a long‐lasting increase in locomotor activity and a lack of reaction to spatial change; both these results are in agreement with the known crucial influence of the septo‐hippocampal cholinergic system in hippocampal functioning. Stimulation of 5‐HT1A and 5‐HT1B receptors induced a decrease in object exploration and habituation without affecting the retrieval of spatial information. But stimulation of hippocampal 5‐HT1B receptors induced a selective change in the animal's emotional state, i.e., an initial decrease in locomotor activity and a neophobic reaction in response to a new object; such effects did not occur following stimulation of 5HT1A receptors. These results have to be considered in the light of the anxiogenic propety of 5‐HT1B agonists. On the whole, they support the hypothesis of the involvement of the serotonergic system, via 5HT1A and 5‐HT1B receptors, in the modulation of hippocampal functions. © 1995 Wiley‐Liss, Inc.
Electrophysiological diversity of pyramidal‐shaped neurons at the granule cell layer/hilus border of the rat dentate gyrus recorded in vitro
Authors: Scharfman Helen E.
Published: May 2005

In the rat dentate gyrus, pyramidal‐shaped cells located on the border of the granule cell layer and the hilus are one of the most common types of γ‐aminobutyric acid (GABA)‐immunoreactive neurons. This study describes their electrophysiological characteristics. Membrane properties, patterns of discharge, and synaptic responses were recorded intracellularly from these cells in hippocampal slices. Each cell was identified as pyramidal‐shaped by injecting the marker Neurobiotin intracellularly (n =17).

In several respects the membrane properties of the sampled cells were similar to “fast‐spiking” cells (putative inhibitory interneurons) that have been described in other areas of the hippocampus. For example, input resistance was high (mean 91.3 megohms), the membrane time constant was short (mean 7.7 ms), and there was a large afterhyperpolarization following a single action potential (mean 10.5 mV at resting potential). However, the action potentials of most pyramidal‐shaped cells were not as brief (mean 1.2 ms total duration) as those of most previously described fast‐spiking cells. Many pyramidal‐shaped neurons had strong spike frequency adaptation relative to other fast‐spiking cells. Although these latter two characteristics were apparent in the majority of the sampled cells, there were exceptional pyramidal‐shaped neurons with fast action potentials and weak adaptation, demonstrating the electrophysiological variability of pyramidal‐shaped cells.

Responses to outer molecular layer stimulation were composed primarily of excitatory postsynaptic potentials (EPSPs) rather than inhibitory postsynaptic potentials (IPSPs), and were usually small (EPSPs evoked at threshold were often less than 2 mV), and brief (less than 30 ms). There was variability, because in a few cells EPSPs evoked at threshold were much larger. However, regardless of EPSP amplitude, suprathreshold stimulation (up to 4 times the threshold stimulus strength) rarely evoked more than one action potential in any cell. The results suggest that stimulation of perforant path axons produces limited excitatory synaptic responses in pyramidal‐shaped neurons. This may be one of the reasons why they are relatively resistant to prolonged perforant path stimulation.

The pyramidal‐shaped neurons located at the base of the granule cell layer have been associated historically with a basket plexus around granule cell somata, and have been called pyramidal “basket” cells. However, basket‐like endings were rare and axon collaterals outside the granule cell layer were common. Many axon collaterals were as far from the granule cell layer as the outer molecular layer and the central hilus, and antidromic action potentials could be recorded in some cells in response to weak stimulation of these areas. Taken together with the electrophysiological variability, the results indicate that these cells are physiologically heterogeneous. © 1995 Wiley‐Liss, Inc.
Co‐localization of somatostatin mRNA and parvalbumin in the dorsal rat hippocampus after cerebral ischemia
Authors: Bering Robert , Diemer Nils Henrik , Draguhn Andreas , Johansen Flemming Fryd
Published: May 2005

Following transient global ischemia most of the neurons containing somatostatin in the fascia dentata of the dorsal hippocampal formation die, while somatostatinergic neurons in the CA1 region survive. These neurons react to ischemia with a transiently reduced expression of somatostatin mRNA and peptide. We have tested the hypothesis that this selective vulnerability is solely related to those somatostatinergic neurons which do not express the calcium‐binding protein parvalbumin. Postischemic changes were studied in rat dorsal hippocampus at 2 and 16 days after 10 min of global cerebral ischemia using a four‐vessel occlusion model. We performed a double‐staining visualizing the mRNA coding for somatostatin by non‐radioactive in situ hybridization and parvalbumin protein by immunocytochemistry. Only 5% of the somatostatinergic cells in the fascia dentata contained parvalbumin. The number of somatostatinergic cells was permanently reduced following ischemia. Among surviving neurons we found cells with and without parvalbumin expression. Thus, expression of parvalbumin is not predictive for survival of somatostatinergic cells in the fascia dentata. In contrast, in CA1, 37% of the somatostatinergic cells contained parvalbumin. These cells were unaffected by the transient ischemic period. The somatostatinergic cells lacking parvalbumin showed transiently reduced mRNA levels at day 2, but recovered to control values at the 16th postischemic day. Thus, expression of the calcium‐buffering protein parvalbumin coincides with resistance of somatostatinergic neurons in CA1 to transient effects of ischemia.

We conclude that the calcium‐buffering capacity of parvalbumin may partially contribute to the protection of somatostatinergic neurons from ischemia in the dorsal hippocampus. However, the survival of somatostatinergic cells without parvalbumin indicates the importance of other factors as well. © 1995 Wiley‐Liss, Inc.
Does electroconvulsive shock therapy work through opioid mechanisms?
Authors: Jackson Helen C. , Nutt David J.
Published: May 2005

It is now well‐established that electroconvulsive shock (ECS) is the most effective treatment for severe depression. Over the past two decades a great deal of new information has been obtained regarding its neuropharmacological basis. The present review examines evidence that the behavioural and mood‐elevating actions of ECS are mediated through changes in the function of opioid receptors or their endogenous transmitters. The recent discovery of stable, non‐peptide ligands for the δK‐ and δ‐receptor subtypes are detailed, and the prospects for a new phase of research in this area are expounded.
Creating equivalent word lists for the Buschke Selective Reminding Test
Authors: Coen R. F. , Kinsella A. , Lambe R. , Kenny M. , Darragh A.
Published: May 2005

During investigation of DUP 996, a novel compound with potential memory‐enhancing properties, nine parallel forms of the Buschke Selective Reminding Test were required. Nine word lists were created using a previously published methodology and word pool. In order to assess the equivalence of these word lists, data on each of the nine test forms were obtained from 21 subjects who received a single placebo dose in closely controlled clinical trial conditions. Analysis of variance revealed between‐subject effect, confirming the large inter‐individual differences in performance which had been observed during testing. The subjects were categorized as poor or good performers, and in a subsequent analysis the test forms were not found to differ significantly within the groups, confirming the utility of the methodology and word pool for the creation of unmatched word lists of similar difficulty.
Schizophrenia: Basic, release, reactive and defect processes
Authors: Healy David
Published: May 2005

Recent development in the classification of schizophrenic psychopathology and research on the mechanism of action of neuroleptic drugs are reviewed in the light of a proposal by Chapman and McGhie in 1963 that schizophrenic morbidity might be significantly reduced by an appropriate cognitive management. It is concluded that current findings in cognitive psychology and neuropsychology support the Chapman and McGhie proposal, but that a clinical application of their proposal requires a recognition of the multidimensionality of positive and negative schizophrenic syndromes. These syndromes, it is suggested, are constituted by underlying basic, release, reactive and defect processes. Basic and release processes, it is postulated, stem from frontal lobe dysfunction. Reactive processes are composed of cognitive distortions of basic and release experiences and should be open to a cognitive management. Defect processes are constituted by coexisting minimal brain dysfunction. This proposal is at odds with the dopamine hypothesis of schizophrenia but is consistent with a dopamine hypothesis of neuroleptic action. The implications of the proposal for both the neuroleptic and non‐neuroleptic pharmacotherapy of schizophrenia are outlined. In particular the development of intermittent pharmacotherapy is noted and the likely significance of emerging cognitive managements for clinical problems for the future assessment of clinical trails of pharmacological agents in schizophrenia.
Effects of tranylcypromine on serotonin content and monoamine oxidase activitity of the human blood platelet
Authors: Oxenkrug Gregory F. , Balon Richard , McCauley Roy B. , McIntyre Iain M.
Published: May 2005

Inhibition (>80 per cent) of platelet monoamine oxidase (MAO‐B type) and and an increase of platelet serotonin content were observed after tranylcypromine administration. It is suggested that the increase in platelet serotonin reflects MAO‐A inhibition, which may be correlated with antidepressant and hypotensive effects of MAO inhibitors.
Relationship between Tardive Dyskinesia and psychopathology in a group of schizophrenic patients attending a rehabilitation centre
Authors: Perenyi A. , Zador G. , Horvath S.
Published: May 2005

Twenty‐five of 76 patients suffering from chronic schizophrenia, treated in a rehabilitation centre, were found to have tardive dyskinesia (TD) according to the Tardive Dyskinesia Research Diagnostic Criteria (Schooler and Kane, 1982). Patients suffering from TD achieved significantly higher total scores on two subscales (affective flattening and blunting and avolition‐apathy, respectively) of the Scale for the Assessment of Negative Symptoms. On the other hand, positive symptoms assessed by the Brief Psychiatric Rating Scale did not distinguish the two groups. Our findings support the idea that patients suffering predominantly from negative symptoms of schizophrenia may have a higher vulnerability for the development of TD than schizophrenic patients showing mainly positive symptoms.
The influence of ageing on serum levels of tertiary tricyclic antidepressants
Authors: Leinonen E. , Ylitalo P.
Published: May 2005

The influence of ageing on serum levels of tertiary tricyclic antidepressants (TCAs) was studied in 385 psychiatric inpatients treated daily with one of three TCAs: 157 patients with amitriptyline (154 ± 47 mg, mean dose ± SD), 183 with doxepin (177 ± 59 mg) and 45 with clomipramine (153 ± 51 mg). The patients were divided into three age groups: 125 of them were aged < 35 years, 218 were 35–65 years and 42 were > 65 years. The numbers of blood samples for gas‐chromatographic monitoring of steady‐state concentrations of serum tertiary and secondary TCAs were 192 for amitriptyline, 240 for doxepin and 138 for clomipramine. The concentrations of serum amitriptyline and nortriptyline rose in an age‐related manner. The serum clomipramine and norclomipramine concentrations were higher in the middle‐aged than in the young patient groups, whereas serum doxepin and nordoxepin concentrations changed less markedly with advancing age. The variations of serum amitriptyline and nortriptyline concentrations were not greater in old patients than in middle‐aged ones. Neither were the variations in doxepin and nordoxepin concentrations enlarged with advancing age (but those in clomipramine and norclomipramine concentrations were wider in middle‐aged than in young patients). The number of too high (‘toxic’) TCA concentrations was inconsistently greater in the elderly than in the two younger age groups. The results suggest that the liability of old patients to the adverse effects of TCAs is not—at least with all TCA treatments—due to the enlarged variation in serum drug levels or to the increased frequency of ‘toxic’ serum TCA concentrations.
EEG mapping central effects of multiple doses of linopirine—a cognitive enhancer—in healthy elderly male subjects
Authors: Saletu B. , Darragh A. , Breuel H. P. , Herrmann W. , Salmon P. , Coen R. , Anderer P.
Published: May 2005

In a double‐blind, placebo‐controlled parallel group study, the encephalatropic effects of multiple doses of linopirine (DUP 996), a novel phenylindolinone derivative enhancing the stimulated release of acetylcholine in cholinergic nerve terminals, but also increasing concentrations of dopamine and serotonin, were investigated in 30 elderly, healthy volunteers. Fifteen subjects were randomly assigned to receive 20 mg DUP 996 b.i.d. and 15 were assigned to receive placebo. The doses were given at 12‐h intervals for 10 days with an additional morning dose on day 11. Multi‐lead EEG recordings were obtained after an adaptation session on day −1, as well as on days 2, 5 and 10 prior to and in the second hour after the morning dose. Computer‐assisted spectral analysis of the EEG and subsequent topographic brain mapping of the drug‐induced EEG changes demonstrated significant central effects of DUP 996, characterized by an augmentation of total power, decrease of delta and theta activity, increase in alpha and beta activity and an acceleration of the centroid. These findings are opposite to those seen in dementias and indicative of an improvement in vigilance, and have also been described with other cognition‐enhancing drugs. Time‐course investigations demonstrated more CNS changes 2 hours after than before morning oral dosing on days 2 and 5. The pharmacodynamic peak was observed in the 2nd hour after dosing on day 2. Topographically, the drug‐induced changes over time were most pronounced over fronto‐temporal, temporo‐occipital, parietal and frontal regions, e.g. over brain areas afflicted most by Alzheimer's disease.
Nocturnal and next‐day effects of ethanol and basal level of sleepiness
Authors: Roehrs T. , Yoon J. , Roth T.
Published: May 2005

Five healthy young men (mean age 25.6 years) consumed ethanol (0.8 g/kg producing breath ethanol concentration (BEC) of 0.06 per cent on average 30 min post‐consumption) and placebo at 2200–2230 h after 4 and 8 h in bed (TIB) the previous night. Standard sleep recordings were collected from 2300 to 0700 h. The next‐day latency to sleep onset was tested at 1000, 1200, 1400 and 1600 h and divided attention performance and hangover symptoms were assessed 30 min after each latency test. The 4 h TIB increased sleep efficiency, but did not interact with the effects of ethanol. Ethanol altered sleep staging. In analyses of ethanol effects by halves of the night, ethanol increased percentage stage 3/4 sleep in the first half and increased percentage stage 1 sleep in the second half. The following day, mean daily sleep latency (MSLT) was reduced and mean divided attention tracking errors were increased with ethanol. Ethanol effects (mild) on the hangover questionnaire were detected only on the 0800 h assessment.
Topographic pharmaco‐EEG mapping of increasing doses of buspirone and its comparison with diazepam
Authors: Barbanoj M. J. , Anderer P. , Antonijoan R. M. , Torrent J. , Saletu B. , Jané F.
Published: May 2005

It has been argued that representative drugs of the main psychopharmacological classes induce similar pharmaco‐EEG changes within groups but different changes between groups. The aim of this double‐blind, cross‐over, placebocontrolled study was to evaluate the effects of single oral doses of buspirone (BUS) 5, 15 and 30 mg in 15 healthy young subjects of both sexes on topographic maps of quantiative pharmaco‐EEG, using diazepam (DZP) 10 mg as reference compound. Sixteen lead recordings of three‐minute vigilance‐controlled EEG (V‐EEG) and four‐minute resting EEG (R‐EEG) were assessed at 0, 1, 2, 4, 6 and 8 hours after drug intake. EOG activity (vertical and horizontal) was also recorded in order to minimize ocular artifacts before applying an automatic artifact rejection method. MANOVA/Hotelling T2 maps (multivariate analysis) showed a highly significant differentiation of DZP from placebo from the 1 st until the 8th hour all over the brain. After BUS a clear dose‐response was observed with effects being greater and longer lasting with increasing doses, the highest showing a peak effect in the 2nd hour which lasted until the 4th hour, mostly in central regions. Maps of drug‐induced pharmaco‐EEG changes as compared to placebo‐induced alterations (univariate analysis) demonstrated typical ‘anxiolytic pharmaco‐EEG patterns’ after DZP, characterized by a decrease of total power, attenuation of alpha activity and augmentation of beta activity, as well as by an increase of the centroid and centroid deviation of the total activity. Furthermore, a decrease of the centroid of the combined delta‐theta activity and an increase of the centroid of alpha activity was seen. In contrast, BUS produced an increase of theta activity with an acceleration of the centroid of the combined delta‐theta activity, no modification of alpha activity but a slowing down of its centroid and a tendency to reduce beta activity. The centroid of the total activity was also decreased. Although both compounds have proven their ability to reduce anxiety in patients, their different neurophysiological profiles suggest different neurobiological mechanisms of action after acute administration.
Psychometric aspects of antihistamines: A review
Authors: Rombaut N. E. I. , Hindmarch I.
Published: May 2005

An extensive review of the literature was performed in order to identify those psychometric variables and conditions which have proved to be sensitive to the CNS effects of antihistamines. It is hoped that the result of this review will allow the formulation of a series of guidelines which would be useful both to researchers, when deciding on the methodology of future trials, and to readers when assessing the validity of a particular volunteer study with a antihistamine.
Cholinergic and adrenergic function in depressed and healthy subjects: A neuroendocrine test battery using the growth hormone axis
Authors: O'Keane Veronica , Dinan Timothy G.
Published: May 2005

The two neurotransmitters noradrenaline (NA) and acetylcholine (ACh), both important modulators of GH secretion, have been hypothesised to be reciprocally dysfunctional in depressive illness. This study tested the Adrenergic/Cholinergic Imbalance Hypothesis by comparing GH responses to (a) the cholinesterase inhibitor pyridostigmine and (b) the indirect noradrenergic agonist desipramine in a depressed group (n = 9) and a matched control group. The depressed patients fulfilled criteria for DSM‐111‐R diagnosis of Major Depression: Melancholic Subtype. Three GH challenge tests were administered in each subject: desipramine, pyridostigmine and GH‐releasing hormone (GHRH). The latter was performed to determine pituitary reserve. Each subject also had a dexamethasone suppression test. GH responses (as measured by peak minus baseline values) to GHRH were significantly blunted in the depressed (26·1 ± 4·9 mU/L) compared to the control group (48·4 ± 4·9 m U/L: t = 2·2, df = 16, p < 0·05); and were positively correlated to desipramine/GH responses in both the depressed and control groups (p < 0·001). Peak GH responses to pyridostigmine were relatively increased in the depressed sample (12·2 ± 1·8 m U/L Vs 6·9 ± 1·5 m U/L; t 2·5, df = 16, p < 0·05). Within the depressed group, dexamethasone non‐suppressors had blunted GH responses to desipramine compared to those who cortisol suppressed (p < 0·05). These findings (a) lend some support to the ‘Cholinergic/Adrenergic Imbalance Hypothesis’, (b) suggest that desipramine may bring about the release of GH via the GHRH pathway and (c) blunting of the desipramine/GH response is associated with hypercortisolaemia.
The effect of salbutamol on mood in normal subjects
Authors: Menkes David B. , Fawcett J. Paul , Nunn Megan R. , Boothman‐Burrell David
Published: May 2005

The beta‐2‐adrenoceptor agonist salbutamol, widely used in the treatment of asthma, is thought to have antidepressant activity and possibly an abuse liability. In order to examine the mood‐altering potential of this drug, a placebocontrolled, double‐blind crossover trial was conducted in 21 psychiatrically normal subjects. The Profile of Mood States (POMS) was used to assess mood at baseline, after six weeks of placebo and salbutamol treatment (in either order), and after a four‐week washout period in between treatments. The results showed little difference between treatments, apart from a tendency for salbutamol to worsen subjective mood relative to placebo during the first treatment phase only. In conclusion, the blinded, placebo‐controlled administration of salbutamol gives no evidence of mood‐elevating or addictive properties in psychiatrically normal individuals.