A comparison of impulsive and instrumental subgroups of batterers

The physiological interactions between the dentate gyrus (DG) and CA3 were studied in urethane-anesthetized rats by using field potential recording and current source density (CSD) analysis. Stimulation of CA3b resulted in a short-latency (<2.5-ms onset latency) antidromic population spike in both the DG and CA3c. An excitation (current sink) at the middle molecular layer (MML) was observed at 3-ms latency, possibly mediated by the backfiring of perforant path fibers that projected to both DG and CA3. CA3 stimulation also resulted in a sink at the dendritic layers of CA3c, which was likely mediated by excitatory CA3 recurrent collaterals. It was inferred that the DG was excited at the inner molecular layer (IML) after stimulation near the CA3b/CA3c border. This IML excitation (sink) probably resulted from orthodromic CA3 or hilar projections to the IML and not from mossy fiber backfiring. The IML and the CA3c dendritic sinks were blocked by an intracerebroventricular injection of a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione, but not by a gamma-aminobutyric acid type A (GABA(A)) receptor antagonist, bicuculline. CA3b stimulation evoked population spike bursts (3-7-ms latency) in both DG and CA3c when GABA(A) inhibition was suppressed by bicuculline, thus confirming that the excitatory afferents project from CA3b to DG and CA3c. A CA3 conditioning stimulus pulse given 30-200 ms before a perforant-path test pulse increased the amplitude of the perforant-path-evoked DG population spike (as compared with the test response without conditioning). After a moderate-intensity stimulation of CA3, a late (<20-ms latency) excitation of the MML of the DG was found. The late DG excitation was blocked by procaine injection at the medial perforant path, suggesting its origin from the medial entorhinal cortex. In conclusion, rich interactions between CA3 and other hippocampal structures were studied quantitatively by CSD analysis in vivo. We infer that CA3 provides an early excitatory feedback path to DG through recurrent collaterals or hilar interneurons and a late feedback through the medial entorhinal cortex.     

Transplanted embryonic entorhinal neurons make functional synapses in adult host hippocampus

Grafts of embryonic entorhinal cortex (EC) or non-entorhinal cortex (NEC) were placed into the hippocampus of adult rats with transection of the perforant paths. Graft-host connectivity was investigated at 4-6 months post-transplantation by recording extracellular evoked responses in hippocampal slice preparations. Electrical stimulation of the grafts evoked excitatory postsynaptic potentials (EPSPs) in the outer molecular layer of the dentate gyrus, and the stratum lacunosum moleculare of CA1, CA3, and elicited population spikes in the granule cell layer and the pyramidal cell layer of CA1, but not CA3. While the latencies and the forms of these evoked response were similar to those in matched control slices from the normal animals, the amplitudes were smaller than normal controls. However, in the slices with NEC grafts, no such responses were recorded when stimulus was applied in similar position in the grafts. The findings suggest that grafted entorhinal neurons make viable synaptic connections with the host hippocampus.     

Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation

The hippocampal formation of Mongolian gerbils expresses high amounts of atypical angiotensin II type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific [35S]-labeled riboprobes and by receptor autoradiography using [125I]Sarcosine1-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidal cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfields, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression.     

Relative contributions of thalamic reticular nucleus neurons and intrinsic interneurons to inhibition of thalamic neurons projecting to the motor cortex

1. Intracellular responses to stimulation of the cerebral cortex (Cx) and cerebellum were analyzed in thalamocortical neurons (TCNs) in the ventroanterior-ventrolateral (VA-VL) complex of the thalamus and neurons in the thalamic reticular nuclei (RNs) of anesthetized cats, and the contribution of reticular nucleus neurons (RNNs) and thalamic interneurons (TINs) to cerebral and cerebellar inhibition of TCNs was determined. 2. Single TCNs projecting to area 4 or 6 received convergent monosynaptic excitatory and disynaptic inhibitory inputs from both the dentate nucleus (DN) and the interpositus nucleus (IN). These TCNs also received monosynaptic excitatory postsynaptic potentials (EPSPs) and disynaptic inhibitory postsynaptic potentials (IPSPs) from the pericruciate cortex (areas 4 and 6). Each TCN received the strongest excitatory and inhibitory inputs from the cortical area to which that TCN projected, and weaker inhibitory inputs from adjacent cortical areas. 3. RNNs were identified morphologically by intracellular injection of horseradish peroxidase (HRP). Stimulation of the brachium conjunctivum (BC) evoked disynaptic EPSPs with a long decay phase in RNNs in the anterior ventrolateral part of the RN. Single RNNs received convergent disynaptic excitatory inputs from both the DNA and the IN. Stimulation of the Cx produced monosynaptic long-lasting EPSPs with two different latencies in these RNNs: early EPSPs with latencies of 0.9-2.1 ms and late EPSPs with latencies of 1.8-3.5 ms. Collision experiments with BC- and Cx-evoked EPSPs in RNNs indicated that BC-evoked disynaptic EPSPs and Cx-evoked early EPSPs were produced by axon collaterals of TCNs to RNNs. The latencies of the Cx-evoked late EPSPs in RNNs were almost identical to those of Cx-evoked monosynaptic EPSPs in TCNs, indicating that corticothalamic neurons (CTNs) exert monosynaptic excitatory effects on RNNs and TCNs. 4. Stimulation of the Cx produced IPSPs in TCNs with short latencies of 1.8-2.7 ms and longer latencies of > or = 2.8 ms. The Cx-evoked early IPSPs with latencies of 1.8-2.7 ms were mediated by RNNs. The origin of Cx-evoked late IPSPs with latencies of > or = 2.8 ms in TCNs was twofold, Cx-induced early IPSPs in TCNs were facilitated by conditioning cortical stimulation that induced late IPSPs in the TCNs. The same conditioning cortical stimulation also facilitated BC-evoked disynaptic IPSPs. The time course of this facilitatation indicated that CTNs produce long-lasting excitation in TINs. These results indicated that Cx-evoked IPSPs with latencies of > 2.7 ms were mediated at least in part by RNNs and inhibitory TINs in the VA-VL complex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

Epileptic afterdischarge in the hippocampal-entorhinal system: current source density and unit studies

The contribution of the various hippocampal regions to the maintenance of epileptic activity, induced by stimulation of the perforant path or commissural system, was examined in the awake rat. Combination of multiple-site recordings with silicon probes, current source density analysis and unit recordings allowed for a high spatial resolution of the field events. Following perforant path stimulation, seizures began in the dentate gyrus, followed by events in the CA3-CA1 regions. After commissural stimulation, rhythmic bursts in the CA3-CA1 circuitry preceded the activation of the dentate gyrus. Correlation of events in the different subregions indicated that the sustained rhythmic afterdischarge (2-6 Hz) could not be explained by a cycle-by-cycle excitation of principal cell populations in the hippocampal-entorhinal loop. The primary afterdischarge always terminated in the CA1 region, followed by the dentate gyrus, CA3 region and the entorhinal cortex. The duration and pattern of the hippocampal afterdischarge was essentially unaffected by removal of the entorhinal cortex. The emergence of large population spike bursts coincided with a decreased discharge of interneurons in both CA1 and hilar regions. The majority of hilar interneurons displayed a strong amplitude decrement prior to the onset of population spike phase of the afterdischarge. These findings suggest that (i) afterdischarges can independently arise in the CA3-CA1 and entorhinal dentate gyrus circuitries, (ii) reverberation of excitation in the hippocampal-entorhinal loop is not critical for the maintenance of afterdischarges and (iii) decreased activity of the interneuronal network may release population bursting of principal cells.     

An autoradiographic study of the development of the entorhinal and commissural afferents to the dentate gyrus of the rat

The development of the entorhinal, ipsilateral associational, and commissural afferents to the dentate gyrus have been studied autoradiographically, following the injection of small amounts of tritiated proline into the medial and lateral parts of the entorhinal cortex, and into fields CA3c and CA4 of the hippocampus, in a series of rats, on the third, sixth, and twelfth postnatal days. Clear labeling of the entorhinal afferents were found at the third postnatal day, and from the earliest stage studied the afferents from the two parts of the entorhinal cortex appear to be spatially segregated within the stratum moleculare of the dentate gyrus: the fibers from the lateral entorhinal area occupying the outermost one-third, or so, of this stratum, while those from the medial entorhinal cortex occupy its middle zone. The ipsilateral hippocampo-dentate associational pathway is present at the third postnatal day, but the commissural projection (which shares with it the inner part of the stratum moleculare) could not be labeled until the sixth postnatal day. By the twelfth day the characteristic adult pattern of distribution of the terminals of the two hippocampo-dentate pathways is established. Although this pattern is best accounted for on the basis of a temporal competition for the available synaptic sites on the proximal parts of the dendrites of the granule cells, the spatial segregation of these two fiber systems from those arising in the entorhinal cortex, is probably due to the selective fasciculation of fibers in each group of afferents and to their early cytochemical specificity.     

Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia

The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.     

Precocious development of parvalbumin-like immunoreactive interneurons in the hippocampal formation and entorhinal cortex of the fetal cynomolgus monkey

The calcium-binding protein parvalbumin (PV), a reliable marker of the hippocampal basket and chandelier cells, is first expressed on embryonic day 83 (E83), corresponding to midgestation of the macaque monkey, in restricted hippocampal groups of immature neurons (Berger and Alvarez [1996] J. Comp. Neurol. 366:674-699). In the present study, PV-like immunoreactivity (LIR) was used to follow the further development of this subclass of interneurons. Asynchronous area-specific developmental sequences were observed, predominating initially in the caudal half of the hippocampal formation and the laterocaudal division of the entorhinal cortex and occurring relatively simultaneously in the interconnected hippocampal and entorhinal subfields. Dendritic elongation of PV-like immunoreactive interneurons and perisomatic distribution of PV-like immunoreactive terminal boutons on their cellular targets were first observed in the subiculum around E127; then from E127 to E142 in CA3/CA2 and layers III-V of the entorhinal cortex and, to a lesser extent in CA1, the dentate hilus and deep granule cell layer; and finally from E156 to postnatal day 12 in the rest of the dentate gyrus, the presubiculum and parasubiculum, and layers III-II-I of the entorhinal cortex. These data provide the first indication that a population of basket cells, a major gamma-aminobutyric acid (GABA)ergic component of the hippocampal intrinsic inhibitory circuitry, reaches its cellular targets several weeks before birth in primates in contrast to rodents. The role of the prenatal PV expression in the hippocampal formation of nonhuman primates and whether it coincides with the onset of postsynaptic inhibitory potentials or is accompanied or preceded by a period of gamma-aminobutyric acid-mediated excitatory effects as in rat pups, are crucial questions. They underline the need to pursue direct investigations on primates to be able to legitimately extrapolate the data obtained in rodents.     

Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss

Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal neuron loss. J. Neurophysiol. 80: 3031-3046, 1998. Synaptic responses of entorhinal cortical and hippocampal neurons were examined in vivo and in vitro, 1 mo to 1.5 yr after a unilateral entorhinal lesion caused by a focal injection of amino-oxyacetic acid (AOAA). It has been shown previously that injection of AOAA into the medial entorhinal cortex produces cell loss in layer III preferentially. Although behavioral seizures stopped approximately 2 h after AOAA treatment, abnormal evoked responses were recorded as long as 1.5 yr later in the entorhinal cortex and hippocampus. In the majority of slices from AOAA-treated rats, responses recorded in the superficial layers of the medial entorhinal cortex to white matter, presubiculum, or parasubiculum stimulation were abnormal. Extracellularly recorded responses to white matter stimulation were prolonged and repetitive in the superficial layers. Intracellular recordings showed that residual principal cells in superficial layers produced prolonged, repetitive excitatory postsynaptic potentials (EPSPs) and discharges in response to white matter stimulation compared with brief EPSPs and a single discharge in controls. Responses of deep layer neurons of AOAA-treated rats did not differ from controls in their initial synaptic response. However, in a some of these neurons, additional periods of excitatory activity occurred after a delay. Abnormal responses were recorded from slices ipsilateral as well as contralateral to the lesioned hemisphere. Recordings from the entorhinal cortex in vivo were abnormal also, as demonstrated by prolonged and repetitive responses to stimulation of the area CA1/subiculum border. Evoked responses of hippocampal neurons, recorded in vitro or in vivo, demonstrated abnormalities in selected pathways, such as responses of CA3 neurons to hilar stimulation in vitro. There was a deficit in the duration of potentiation of CA1 population spikes in response to repetitive CA3 stimulation in AOAA-treated rats. Theta activity was reduced in amplitude in area CA1 and the dentate gyrus of AOAA-treated rats, although evoked responses to angular bundle stimulation could not be distinguished from controls. The results demonstrate that a preferential lesion of layer III of the entorhinal cortex produces a long-lasting change in evoked and spontaneous activity in parts of the entorhinal cortex and hippocampus. Given the similarity of the lesion produced by AOAA and entorhinal lesions in temporal lobe epileptics, these data support the hypothesis that preferential damage to the entorhinal cortex contributes to long-lasting changes in excitability, which could be relevant to the etiology of temporal lobe epilepsy.     

Hippocampal cells have behavioral correlates during the performance of an auditory working memory task in the rat.

Single unit activity was recorded from the rat hippocampal CA1 and CA3 subfields, dentate gyrus (DG), entorhinal cortex, subicular complex, motor cortex (MC), prefrontal cortex, and dorsomedial thalamus during performance of a continuous nonmatching-to-sample task. The rats made go and no-go responses to indicate whether the current tone was the same as (match) or different from (nonmatch) the preceding tone. About half of the units from the MC, CA1, CA3, and DG had motor correlates, increments of activity immediately prior to a go response. This suggests that those regions are involved in making a response. The CA1 and CA3 had more units with comparison–motor correlates, increases of activity prior to a correct go response on nonmatch trials. This pattern of activity suggests that the CA1 and CA3 are involved in a mnemonic process of comparison between retained and current stimuli in a nonspatial auditory task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.     

Differential effects of a benzodiazepine on synaptic transmissions in rat hippocampal neurons in vitro

The effects of midazolam, one of the most popular benzodiazepines, on synaptic transmissions were compared with intracellular recordings between CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) in rat hippocampal slices. First, we studied the effects of midazolam on orthodromically evoked spikes, membrane properties and synaptic potentials. Secondly, the effects of a GABA(A) receptor agonist, muscimol, were examined on membrane properties to determine whether or not the densities of GABA(A) receptors are different between CA1-PCs and DG-GCs. Midazolam (75 microM) markedly depressed orthodromically evoked spikes in CA1-PCs, compared with those in DG-GCs. A GABA(A) receptor antagonist, bicuculline (10 microM), almost completely antagonized the depressant effects of midazolam on spike generation in CA1-PCs, whereas it had little effect on midazolam in dentate gyrus granule cells. Midazolam produced either depolarizing or hyperpolarizing effects on resting membrane potentials (Vm) with an input resistance decrease in CA1-PCs, whereas it produced depolarized Vm in DG-GCs. Midazolam significantly increased the amplitude of monosynaptic inhibitory postsynaptic potentials in CA1-PCs, whereas midazolam slightly decreased these in DG-GCs. Midazolam significantly decreased the amplitude of excitatory postsynaptic potentials both in CA1-PCs and DG-GCs. Muscimol (100 microM) produced either depolarizing or hyperpolarizing effects on Vm with an input resistance decrease in CA1-PCs, and it depolarized Vm with an input resistance decrease in DG-GCs. These results demonstrate that midazolam has differential effects on excitatory and inhibitory synaptic transmissions in hippocampal neurons. The mechanism of this difference could be partly due to the different types of GABA(A) receptors between CA1-PCs and DG-GCs.     

Amplification of perforant-path EPSPs in CA3 pyramidal cells by LVA calcium and sodium channels

The perforant path forms a monosynaptic connection between the cells of layer II of the entorhinal cortex and the pyramidal cells in hippocampal area CA3. Although this projection is prominent anatomically, very little is known about the physiological properties of this input. The distal location of these synapses suggests that somatically recorded perforant-path excitatory postsynaptic potentials (EPSPs) may be influenced by the activation of voltage-dependent channels in CA3 cells. We observed that perforant-path EPSPs are reduced (by approximately 25%) by blockade of postsynaptic low-voltage-activated calcium and sodium channels, indicating that perforant-path EPSPs are amplified by the activation of these channels. These data suggest that the perforant path may represent an important and highly modifiable direct connection between the entorhinal cortex and area CA3.     

Block of HFS-induced LTP in the dentate gyrus by 1S,3S-ACPD: further evidence against LTP as a model for learning

We have previously shown that block of high-frequency stimulation (HFS) induced long-term potentiation (LTP) of synaptic transmission in area CA1 by (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD; 5 microliters of a 20 mM solution), an agonist at group II metabotropic glutamate receptors, did not prevent animals from learning a spatial task. Here we show that the same dose of 1S,3S-ACPD also blocked the induction of HFS-induced LTP of the slope of the excitatory postsynaptic potential and of the amplitude of the population spike in the dentate gyrus. We conclude that HFS-induced LTP in the dentate gyrus is not a good model for memory formation.     

Changes in field potentials and membrane currents in rat sensorimotor cortex following repeated tetanization of the corpus callosum in vivo

Repeated, daily tetanization of the corpus callosum induces lasting changes in sensorimotor cortex field potential responses, but the synaptic populations that mediate these responses and support long-term potentiation (LTP) have not been characterized. Current source density analyses of field responses were compared between control animals and those in which LTP was induced by 10 daily series of tetanizations. Tetanization and paired-pulse stimulation (100 ms interval) enhanced the duration of initial (approximately 3 ms onset) deep-negative population spike activity generated by a current sink in layer V that peaked repeatedly at a frequency of approximately 400 Hz. The early (approximately 10 ms to peak) surface-negative component of field responses was generated by a current sink in upper layer V and a source in layer VI. This monosynaptic component followed high stimulation frequencies, recovered quickly from the effects of anaesthesia, and was enhanced by both tetanization and paired-pulse stimulation. The late (approximately 20 ms to peak) surface-negative component was generated by a sink in upper layer V and a source deep in layer V, and was greatly enhanced by tetanization and paired-pulse stimulation. The late component did not follow high-frequency stimulation and recovered slowly from anaesthesia, suggesting that it is driven polysynaptically. Potentiation of monosynaptic thalamic and cortico-cortical afferents probably mediates enhancements of the early component and population spikes, while potentiation of polysynaptic afferents to layer V may contribute to growth in the late component.     

Short-lived intermediates in hemoglobin/O2 systems

By using three-dimensional computer reconstruction techniques and the production of two-dimensional unfolded maps, we analyzed the topographic organization of projections from the entorhinal cortex of the rat to the dentate gyrus. The retrograde tracers, Fast blue and Diamidino yellow, were injected at all septotemporal levels of the dentate gyrus, and the distribution of retrogradely labeled layer II cells in the entorhinal cortex was plotted by using computer-aided microscopy systems. Discrete injections of fluorescent dyes into the dentate gyrus labeled bands of layer II neurons in the entorhinal cortex that covered approximately 45% of its surface area. Injections confined to the septal half of the dentate gyrus resulted in a band that occupied the most lateral and caudomedial portions of the entorhinal cortex. Although there were subtle changes in the density of labeled cells in this region, essentially the same region of cells was labeled after any injection into the septal half of the dentate gyrus. Injections into mid-septotemporal levels of the dentate gyrus (50-75% of the distance from the septal pole) led to a distinctly different pattern of retrograde labeling. A more medial portion of the lateral entorhinal cortex and a more rostral portion of the medial entorhinal area were labeled in these cases. Another change in entorhinal labeling occurred when the injection involved the most temporal quarter of the dentate gyrus. Injections into this area led to a constrained region of entorhinal labeling that included the most medial portion of the lateral entorhinal area and the most rostral portion of the medial entorhinal area. Although the domains of cells projecting to septal, mid-septotemporal, and temporal levels of the dentate gyrus were not entirely segregated, there was relatively little overlap of the three populations of neurons. These data raise the possibility that different portions of the entorhinal-hippocampal circuit are capable of semiautonomous information processing, at least at the stage of input to the dentate gyrus.     

Biochemical analysis of ++Prospero protein during asymmetric cell division: cortical Prospero is highly phosphorylated relative to nuclear Prospero

Hippocampal synapses express two distinct forms of the long-term potentiation (LTP), i.e. NMDA receptor-dependent and -independent LTPs. To understand its molecular-anatomical basis, we produced affinity-purified antibodies against the GluRepsilon1 (NR2A), GluRepsilon2 (NR2B), and GluRzeta1 (NR1) subunits of the N-methyl-D-aspartate (NMDA) receptor channel, and determined their distributions in the mouse hippocampus. Using NMDA receptor subunit-deficient mice as the specificity controls, section pretreatment with proteases (pepsin and proteinase K) was found to be very effective to detect authentic NMDA receptor subunits. As the result of modified immunohistochemistry, all three subunits were detected at the highest level in the strata oriens and radiatum of the CA1 subfield, and high levels were also seen in most other neuropil layers of the CA1 and CA3 subfields and of the dentate gyrus. However, the stratum lucidum, a mossy fibre-recipient layer of the CA3 subfield, contained low levels of the GluRepsilon1 and GluRzeta1 subunits and almost excluded the GluRepsilon2 subunit. Double immunofluorescence with the AMPA receptor GluRalpha1 (GluR1 or GluR-A) subunit further demonstrated that the GluRepsilon1 subunit was colocalized in a subset, not all, of GluRalpha1-immunopositive structures in the stratum lucidum. Therefore, the selective scarcity of these NMDA receptor subunits in the stratum lucidum suggests that a different synaptic targeting mechanism exerts within a single CA3 pyramidal neurone in vivo, which would explain contrasting significance of the NMDA receptor channel in LTP induction mechanisms between the mossy fibre-CA3 synapse and other hippocampal synapses.     

Fast game theory coupled to slow population dynamics: the case of domestic cat populations

The distribution of a metabotropic glutamate receptor mGluR2 in the central nervous system was immunohistochemically examined in the rat and mouse with a monoclonal antibody raised against an N-terminal sequence of rat mGluR2 (amino acid residues 87-134). Neuronal cell bodies with mGluR2-like immunoreactivity (mGluR2-LI) were clearly shown in the horizontal cells of Cajal in the cerebral cortex, neurons in the triangular septal nucleus and medial mammillary nucleus, Golgi cells and the unipolar brush cells in the cerebellar cortex, and Golgi-like and unipolar brush-like cells in the cochlear nucleus. Neuropil was intensely immunostained in the accessory olfactory bulb, bed nucleus of the accessory olfactory tract, neocortex, cingulate cortex, retrosplenial cortex, subicular and entorhinal cortices, stratum lacunosum-moleculare of CA1 and CA3, molecular layer of the dentate gyrus, periamygdaloid cortex, basolateral amygdaloid nucleus, bed nucleus of the anterior commissure, caudate-putamen, accumbens nucleus, thalamic reticular nucleus, anteroventral and paraventricular thalamic nuclei, granular layer of the cerebellar cortex, anterior and ventral tegmental nuclei, granular layer of the cochlear nucleus, and parvicellular part of the lateral reticular nucleus. Many axons in the white matter and fiber bundles were also immunostained. No glial cells with mGluR2-LI were found. No particular species differences were found in the distribution pattern of mGluR2-LI between the rat and mouse. The results indicate that mGluR2 is expressed not only in somato-dendritic domain, but also in axonal domain of excitatory and inhibitory neurons.     

Interaction between superficial layers of the entorhinal cortex and the hippocampus in normal and epileptic temporal lobe

The entorhinal cortex (EC) is a major gateway for sensory information into the hippocampal formation. The information flow from layer II and III of the medial EC to the hippocampus is regulated in a frequency dependent manner. Spread of low Mg2+-induced epileptiform activity from EC to hippocampus differs in slices obtained from normal and kindled rats, and in adult versus juvenile rats. In slices from normal rats, low Mg2+-induced epileptiform activity in the EC had only moderate effects on the areas CA3 and CA1, apparently gated by powerful inhibition in the dentate gyrus. In slices from kindled rats, and from juvenile rats, there is facilitated propagation of the seizure-like events and late recurrent discharges through the EC-hippocampal slice. Temporal lobe epilepsy is associated with selective lesions in layer III of the medial EC. Such loss of layer III cells of the medial EC during epilepsy may contribute to the disturbance of frequency dependent information flow from the EC to the hippocampus, and, therefore, to the cognitive impairments associated with these disorders.