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Area CA1 (area + ca1)
Kinds of Area CA1 Selected AbstractsInterneuron subtype specific activation of mGluR1/5 during epileptiform activity in hippocampusEPILEPSIA, Issue 8 2010Nathalie T Sanon Summary Purpose:, Specific inhibitory interneurons in area CA1 of the hippocampus, notably those located in stratum oriens,alveus (O/A-INs), are selectively vulnerable in patients and animal models of temporal lobe epilepsy (TLE). The excitotoxic mechanisms underlying the selective vulnerability of interneurons have not been identified but could involve group I metabotropic glutamate receptor subtypes (mGluR1/5), which have generally proconvulsive actions and activate prominent cationic currents and calcium responses specifically in O/A-INs. Methods:, In this study, we examine the role of mGluR1/5 in interneurons during epileptiform activity using whole-cell recordings from CA1 O/A-INs and selective antagonists of mGluR1, (LY367385) and mGluR5 (MPEP) in a disinhibited rat hippocampal slice model of epileptiform activity. Results:, Our data indicate more prominent epileptiform burst discharges and paroxysmal depolarizations (PDs) in O/A-INs than in interneurons located at the border of strata radiatum and lacunosum/moleculare (R/LM-INs). In addition, mGluR1 and mGluR5 significantly contributed to epileptiform responses in O/A-INs but not in R/LM-INs. Epileptiform burst discharges in O/A-INs were partly dependent on mGluR5. PDs and associated postsynaptic currents were dependent on both mGluR1, and mGluR5. These receptors contributed differently to postsynaptic currents underlying PDs, with mGluR5 contributing to the fast and slow components and mGluR1, to the slow component. Discussion:, These findings support interneuron subtype-specific activation and differential contributions of mGluR1, and mGluR5 to epileptiform activity in O/A-INs, which could be important for their selective vulnerability in TLE. [source] Propagation Dynamics of Epileptiform Activity Acutely Induced by Bicuculline in the Hippocampal,Parahippocampal Region of the Isolated Guinea Pig BrainEPILEPSIA, Issue 12 2005Laura Uva Summary:,Purpose: Aim of the study is to investigate the involvement of parahippocampal subregions in the generation and in the propagation of focal epileptiform discharges in an acute model of seizure generation in the temporal lobe induced by arterial application of bicuculline in the in vitro isolated guinea pig brain preparation. Methods: Electrophysiological recordings were simultaneously performed with single electrodes and multichannel silicon probes in the entorhinal, perirhinal, and piriform cortices and in the area CA1 of the hippocampus of the in vitro isolated guinea pig brain. Interictal and ictal epileptiform discharges restricted to the temporal region were induced by a brief (3,5 min) arterial perfusion of the GABAA receptor antagonist, bicuculline methiodide (50 ,M). Current source density analysis of laminar field profiles performed with the silicon probes was carried out at different sites to establish network interactions responsible for the generation of epileptiform potentials. Nonlinear regression analysis was conducted on extracellular recordings during ictal onset in order to quantify the degree of interaction between fast activities generated at different sites, as well as time delays. Results: Experiments were performed in 31 isolated guinea pig brains. Bicuculline-induced interictal and ictal epileptiform activities that showed variability of spatial propagation and time course in the olfactory,temporal region. The most commonly observed pattern (n = 23) was characterized by the initial appearance of interictal spikes (ISs) in the piriform cortex (PC), which propagated to the lateral entorhinal region. Independent and asynchronous preictal spikes originated in the entorhinal cortex (EC)/hippocampus and progressed into ictal fast discharges (around 25 Hz) restricted to the entorhinal/hippocampal region. The local generation of fast activity was verified and confirmed both by CSD and phase shift analysis performed on laminar profiles. Fast activity was followed by synchronous afterdischarges that propagated to the perirhinal cortex (PRC) (but not to the PC). Within 1,9 min, the ictal discharge ceased and a postictal period of depression occurred, after which periodic ISs in the PC resumed. Unlike preictal ISs, postictal ISs propagated to the PRC. Conclusions: Several studies proposed that reciprocal connections between the entorhinal and the PRC are under a very efficient inhibitory control (1). We report that ISs determined by acute bicuculline treatment in the isolated guinea pig brain progress from the PC to the hippocampus/EC just before ictal onset. Ictal discharges are characterized by a peculiar pattern of fast activity that originates from the entorhinal/hippocampal region and only secondarily propagates to the PRC. Postictal propagation of ISs to the PRC occured exclusively when an ictal discharge was generated in the hippocampal/entorhinal region. The results suggest that reiteration of ictal events may promote changes in propagation pattern of epileptiform discharges that could act as trigger elements in the development of temporal lobe epilepsy. [source] Enhanced synaptic excitation,inhibition ratio in hippocampal interneurons of rats with temporal lobe epilepsyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007F. Stief Abstract A common feature of all epileptic syndromes is the repetitive occurrence of pathological patterns of synchronous neuronal activity, usually combined with increased neuronal discharge rates. Inhibitory interneurons of the hippocampal formation control both neuronal synchronization as well as the global level of activity and are therefore of crucial importance for epilepsy. Recent evidence suggests that changes in synaptic inhibition during temporal lobe epilepsy are rather specific, resulting from selective death or alteration of interneurons in specific hippocampal layers. Hence, epilepsy-induced changes have to be analysed separately for different types of interneurons. Here, we focused on GABAergic neurons located at the border between stratum radiatum and stratum lacunosum-moleculare of hippocampal area CA1 (SRL interneurons), which are included in feedforward inhibitory circuits. In chronically epileptic rats at 6,8 months after pilocarpine-induced status epilepticus, frequencies of spontaneous and miniature inhibitory postsynaptic currents were reduced, yielding an almost three-fold increase in excitation,inhibition ratio. Consistently, action potential frequency of SRL interneurons was about two-fold enhanced. Morphological alterations of the interneurons indicate that these functional changes were accompanied by remodelling of the local network, probably resulting in a loss of functional inhibitory synapses without conceivable cell death. Our data indicate a strong increase in activity of interneurons in dendritic layers of the chronically epileptic CA1 region. This alteration may enhance feedforward inhibition and rhythmogenesis and , together with specific changes in other interneurons , contribute to seizure susceptibility and pathological synchronization. [source] Metaplasticity of the late-phase of long-term potentiation: a critical role for protein kinase A in synaptic taggingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Jennie Z. Young Abstract The late-phase of long-term potentiation (L-LTP) in hippocampal area CA1 requires gene expression and de novo protein synthesis but it is expressed in an input-specific manner. The ,synaptic tag' theory proposes that gene products can only be captured and utilized at synapses that have been ,tagged' by previous activity. The mechanisms underlying synaptic tagging, and its activity dependence, are largely undefined. Previously, we reported that low-frequency stimulation (LFS) decreases the stability of L-LTP in a cell-wide manner by impairing synaptic tagging. We show here that a phosphatase inhibitor, okadaic acid, blocked homosynaptic and heterosynaptic inhibition of L-LTP by prior LFS. In addition, prior LFS homosynaptically and heterosynaptically impaired chemically induced synaptic facilitation elicited by forskolin/3-isobutyl-1-methylxanthine, suggesting that there is a cell-wide dampening of cAMP/protein kinase A (PKA) signaling concurrent with phosphatase activation. We propose that prior LFS impairs expression of L-LTP by inhibiting synaptic tagging through its actions on the cAMP/PKA pathway. In support of this notion, we show that hippocampal slices from transgenic mice that have genetically reduced hippocampal PKA activity display impaired synaptic capture of L-LTP. An inhibitor of PKA, KT-5720, also blocked synaptic capture of L-LTP. Moreover, pharmacological activation of the cAMP/PKA pathway can produce a synaptic tag to capture L-LTP expression, resulting in persistent synaptic facilitation. Collectively, our results show that PKA is critical for synaptic tagging and for input-specific L-LTP. PKA-mediated signaling can be constrained by prior episodes of synaptic activity to regulate subsequent L-LTP expression and perhaps control the integration of multiple synaptic events over time. [source] NMDA receptor-mediated metaplasticity during the induction of long-term depression by low-frequency stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Bruce Mockett Abstract Metaplasticity refers to the activity-dependent modification of the ability of synapses to undergo subsequent synaptic plasticity. Here, we have addressed the question of whether metaplasticity contributes to the induction of long-term depression (LTD) by low-frequency stimulation (LFS). The experiments were conducted using standard extracellular recording techniques in stratum radiatum of area CA1 in hippocampal slices made from adult Sprague,Dawley rats. The degree of LTD induction was found to be a nonlinear function of the number of pulses during a 1-Hz LFS. Little LTD was observed following 600 or 900 pulses, but a significant LTD occurred following 1200 pulses of LFS, whether delivered in one episode, or in two bouts of 600 pulses given 10 min apart. A similar pattern was observed for 3 Hz LFS. The data support the suggestion that pulses occurring early in the LFS train prime synapses for LTD induction, as triggered by later occurring stimuli. The priming effect lasted at least 120 min, when tested by giving two bouts of 1 Hz LFS (600 pulses each) at different intervals. Neither heterosynaptic nor homosynaptic stimulation by itself was sufficient to prime LTD. However, a combination of the stimuli, induced by increased stimulus strength during the LFS, appeared necessary for inducing the effect. An N -methyl- d -aspartate (NMDA) receptor antagonist markedly reduced total LTD induction, regardless of whether it was administered during the first or second LFS in a protocol employing two bouts of 600 pulse LFS, 30 min apart. These findings strongly support the hypothesis that NMDA receptor-dependent metaplasticity processes contribute to the induction of LTD during standard LFS protocols. [source] Glutamate spillover augments GABA synthesis and release from axodendritic synapses in rat hippocampusHIPPOCAMPUS, Issue 1 2010Misty M. Stafford Abstract Tight coupling between gamma-aminobutyric acid (GABA) synthesis and vesicle filling suggests that the presynaptic supply of precursor glutamate could dynamically regulate inhibitory synapses. Although the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) has been proposed to mediate such a metabolic role, highly efficient astrocytic uptake of synaptically released glutamate normally maintains low-extracellular glutamate levels. We examined whether axodendritic inhibitory synapses in stratum radiatum of hippocampal area CA1, which are closely positioned among excitatory glutamatergic synapses, are regulated by synaptic glutamate release via presynaptic uptake. Under conditions of spatially and temporally coordinated release of glutamate and GABA within pyramidal cell dendrites, blocking glial glutamate uptake enhanced quantal release of GABA in a transporter-dependent manner. These physiological findings correlated with immunohistochemical studies revealing expression of EAAT3 by interneurons and uptake of D-asparate into putative axodendritic inhibitory terminals only when glial uptake was blocked. These results indicate that spillover of glutamate between adjacent excitatory and inhibitory synapses can occur under conditions when glial uptake incompletely clears synaptically released glutamate. Our anatomical studies also suggest that perisomatic inhibitory synapses, unlike synapses within dendritic layers of hippocampus, are not capable of glutamate uptake and therefore transporter-mediated dynamic regulation of inhibition is a unique feature of axodendritic synapses that may play a role in maintaining a homeostatic balance of inhibition and excitation. © 2009 Wiley-Liss, Inc. [source] Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze taskHIPPOCAMPUS, Issue 5 2007Robbert Havekes Abstract It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y-maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus-dependent long-term memory is the adenosine 3,,5, cyclic monophosphate dependent protein kinase (PKA). Here, we examined region-specific changes in immunoreactivity (ir) of the regulatory II,,, subunits of PKA (PKA RII,,,-ir) in the hippocampus during various stages of spatial learning in a Y-maze reference task. Thereafter, we compared changes in hippocampal PKA RII,,,-ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RII,,,-ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RII,,,-ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RII,,,-ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RII,,, protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region-specific changes in hippocampal PKA RII,,,-ir and suggest a differential involvement of hippocampal subregions in match-mismatch detection in case of Y-maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match-mismatch detection. © 2007 Wiley-Liss, Inc. [source] Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injuryHIPPOCAMPUS, Issue 6 2006E. Schwarzbach Abstract Traumatic brain injury (TBI) is a significant health issue that often causes enduring cognitive deficits, in particular memory dysfunction. The hippocampus, a structure crucial in learning and memory, is frequently damaged during TBI. Since long-term potentiation (LTP) is the leading cellular model underlying learning and memory, this study was undertaken to examine how injury affects area CA1 LTP in mice using lateral fluid percussion injury (FPI). Brain slices derived from FPI animals demonstrated an inability to induce LTP in area CA1 7 days postinjury. However, area CA1 long-term depression could be induced in neurons 7 days postinjury, demonstrating that some forms of synaptic plasticity can still be elicited. Using a multidisciplined approach, potential mechanisms underlying the inability to induce and maintain area CA1 LTP were investigated. This study demonstrates that injury leads to significantly smaller N -methyl- D -aspartate potentials and glutamate-induced excitatory currents, increased dendritic spine size, and decreased expression of ,-calcium calmodulin kinase II. These findings may underlie the injury-induced lack of LTP and thus, contribute to cognitive impairments often associated with TBI. Furthermore, these results provide attractive sites for potential therapeutic intervention directed toward alleviating the devastating consequences of human TBI. © 2006 Wiley-Liss, Inc. [source] Individual differences in spatial memory among aged rats are related to hippocampal PKC, immunoreactivityHIPPOCAMPUS, Issue 2 2002Paul J. Colombo Abstract We reported previously that the extent of spatial memory impairment among aged rats was correlated positively with levels of protein kinase C, in hippocampal homogenates measured by quantitative Western blotting (Colombo et al., 1997). In the current study, immunocytochemistry was used to test whether the relationship between elevated PKC, and memory impairment among aged rats could be localized further within regions of the hippocampus. Six- and 24-month-old male Long-Evans rats were first trained in the water maze on a standard place-learning task and then trained 2 weeks later on a transfer task designed for rapid acquisition. In comparison with young rats, aged rats with impaired spatial memory had increased PKC,-immunoreactivity (PKC,-ir) in CA1 of the hippocampus, but not the dentate gyrus. In addition, PKC,-ir in CA1 was correlated positively with spatial memory impairment among aged rats on the standard place-learning and the transfer training tasks. The current results are consistent with our previous report of PKC, in hippocampal homogenates, and show further that the relationships between PKC,-ir and memory impairments among aged rats are most evident in area CA1. Thus age-related impairments of spatial memory, as well as deficits in the flexible use of previously acquired information, may result from dysregulation of PKC,. Hippocampus 2002;12:285,289. © 2002 Wiley-Liss, Inc. [source] High-resolution real-time recording with microelectrode biosensors reveals novel aspects of adenosine release during hypoxia in rat hippocampal slicesJOURNAL OF NEUROCHEMISTRY, Issue 6 2003B. G. Frenguelli Abstract We have used improved miniaturized adenosine biosensors to measure adenosine release during hypoxia from within the CA1 region of rat hippocampal slices. These microelectrode biosensors record from the extracellular space in the vicinity of active synapses as they detect the synaptic field potentials evoked in area CA1 by stimulation of the afferent Schaffer collateral-commissural fibre pathway. Our new measurements demonstrate the rapid production of adenosine during hypoxia that precedes and accompanies depression of excitatory transmission within area CA1. Simultaneous measurement of adenosine release and synaptic transmission gives an estimated IC50 for adenosine on transmission in the low micromolar range. However, on reoxygenation, synaptic transmission recovers in the face of elevated extracellular adenosine and despite a post-hypoxic surge of adenosine release. This may indicate the occurrence of apparent adenosine A1 receptor desensitization during metabolic stress. In addition, adenosine release is unaffected by pharmacological blockade of glutamate receptors and shows depletion on repeated exposure to hypoxia. Our results thus suggest that adenosine release is not a consequence of excitotoxic glutamate release. The potential for adenosine A1 receptor desensitization during metabolic stress implies that its prevention may be beneficial in extending adenosine-mediated neuroprotection in a variety of clinically relevant conditions. [source] Coincidence detection of convergent perforant path and mossy fibre inputs by CA3 interneuronsTHE JOURNAL OF PHYSIOLOGY, Issue 11 2008Eduardo Calixto We performed whole-cell recordings from CA3 s. radiatum (R) and s. lacunosum-moleculare (L-M) interneurons in hippocampal slices to examine the temporal aspects of summation of converging perforant path (PP) and mossy fibre (MF) inputs. PP EPSPs were evoked from the s. lacunosum-moleculare in area CA1. MF EPSPs were evoked from the medial extent of the suprapyramidal blade of the dentate gyrus. Summation was strongly supralinear when examining PP EPSP with MF EPSP in a heterosynaptic pair at the 10 ms ISI, and linear to sublinear at longer ISIs. This pattern of nonlinearities suggests that R and L-M interneurons act as coincidence detectors for input from PP and MF. Summation at all ISIs was linear in voltage clamp mode demonstrating that nonlinearities were generated by postsynaptic voltage-dependent conductances. Supralinearity was not detected when the first EPSP in the pair was replaced by a simulated EPSP injected into the soma, suggesting that the conductances underlying the EPSP boosting were located in distal dendrites. Supralinearity was selectively eliminated with either Ni2+ (30 ,m), mibefradil (10 ,m) or nimodipine (15 ,m), but was unaffected by QX-314. This pharmacological profile indicates that supralinearity is due to recruitment of dendritic T-type Ca2+channels by the first subthreshold EPSP in the pair. Results with the hyperpolarization-activated (Ih) channel blocker ZD 7288 (50 ,m) revealed that Ih restricted the time course of supralinearity for coincidently summed EPSPs, and promoted linear to sublinear summation for asynchronous EPSPs. We conclude that coincidence detection results from the counterbalanced activation of T-type Ca2+ channels and inactivation of Ih. [source] Effects of 4-week Treatment with Lithium and Olanzapine on Levels of Brain-derived Neurotrophic Factor, B-Cell CLL/Lymphoma 2 and Phosphorylated Cyclic Adenosine Monophosphate Response Element-binding Protein in the Sub-regions of the HippocampusBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Michael D. Hammonds It has been suggested that up-regulation of neurotrophic and neuroprotective factors including brain-derived neurotrophic factor (BDNF) and B-cell CLL/lymphoma 2 (Bcl-2) may underlie these neuroplastic actions of the drug. Olanzapine, an atypical anti-psychotic drug, has been shown to be an effective mood stabilizer. Olanzapine also has neurotrophic and neuroprotective actions, and these actions may underlie the efficacy of the drug for bipolar disorder and schizophrenia. However, the molecular mechanism by which the drug produces the neuroplastic actions is poorly understood. To understand a common molecular mechanism underlying the neuroplastic actions of lithium and olanzapine, we assessed the effect of 4-week lithium and olanzapine treatment on the levels of BDNF, Bcl-2 and cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor involved in expression of BDNF and Bcl-2, in the dentate gyrus and hippocampal area CA1. Our results show that 4-week treatment with both olanzapine and lithium increases the levels of Bcl-2 and CREB in the dentate gyrus and hippocampal area CA1. Four-week lithium treatment up-regulates BDNF in the dentate gyrus, and 4-week olanzapine treatment marginally did so. Neither drug altered BDNF levels in area CA1. These results suggest that the up-regulation of Bcl-2 and CREB may underlie the neuroplastic actions of olanzapine and lithium. [source] Effects of Subchronic Lithium Treatment on Levels of BDNF, Bcl-2 and Phospho-CREB in the Rat HippocampusBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2007Michael D. Hammonds Few studies have examined the effects of lithium exposure on the regulation of these molecules in the dentate gyrus (DG) and area CA1 in the hippocampus. We examined the effects of subchronic lithium treatment on the levels of BDNF, Bcl-2 and phosphorylated CREB in the DG and area CA1. We administered LiCl intraperitoneally (1 mEq/kg per day) to adult rats for 14 days, killed animals in 24 hr after the last administration of the drug, and determined the tissue levels of BDNF, Bcl-2 and pCREB in the DG and area CA1. Subchronic lithium treatment for 14 days did not significantly alter the levels of BDNF, Bcl-2 or phosphorylated CREB in the DG and area CA1 in the hippocampus. This study indicates that the lithium-induced up-regulation of these molecules may be various depending on the duration of lithium exposure and particular brain regions exposed to the drug. [source] Parvalbumin-, calbindin-, and calretinin-immunoreactive hippocampal interneuron density in autismACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010Y. A. Lawrence Lawrence YA, Kemper TL, Bauman ML, Blatt GJ. Parvalbumin-, calbindin-, and calretinin-immunoreactive hippocampal interneuron density in autism. Acta Neurol Scand: 2010: 121: 99,108. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background ,, There has been a long-standing interest in the possible role of the hippocampus in autism and both postmortem brain and neuroimaging studies have documented varying abnormalities in this limbic system structure. Aims ,, This study investigates the density of subsets of hippocampal interneurons, immunostained with the calcium binding proteins, calbindin (CB), calretinin (CR) and parvalbumin (PV) to determine whether specific subpopulations of interneurons are impacted in autism. Materials and methods ,, Unbiased stereological techniques were used to quantify the neuronal density of these immunoreactive subpopulations of gamma-aminobutyric acid-ergic (GABAergic) interneurons analyzed in the CA and subicular fields in postmortem brain material obtained from five autistic and five age-, gender- and postmortem interval-matched control cases. Results ,, Results indicate a selective increase in the density of CB-immunoreactive interneurons in the dentate gyrus, an increase in CR-immunoreactive interneurons in area CA1, and an increase in PV-immunoreactive interneurons in areas CA1 and CA3 in the hippocampus of individuals with autism when compared with controls. Discussion/conclusions ,, Although our sample size is small, these findings suggest that GABAergic interneurons may represent a vulnerable target in the brains of individuals with autism, potentially impacting upon their key role in learning and information processing. These preliminary findings further suggest the need for future more expanded studies in a larger number of postmortem brain samples from cases of autism and controls. [source] | |||||||||||||