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G Buzsáki

Publications and source records attributed to G Buzsáki.

At least 19 recordsLinked to original sources
PubMed2006

Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus.

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization.

Adult↗
PubMed2005

Developmental emergence of hippocampal fast-field "ripple" oscillations in the behaving rat pups.

Sharp wave and associated fast oscillatory ripples (140-200 Hz) in the cornu ammonis 1 region are the most synchronous hippocampal patterns in the adult rat. Spike sequences associated with sharp waves are believed to play a critical role in transferring transient memories from the hippocampus to the neocortex and the emergence of superfast ripples is pathognostic in temporal lobe epilepsy. Sharp waves in cornu ammonis 1 stratum radiatum are induced by a strong depolarization by the cornu ammonis 3 Schaffer collaterals, due to the synchronous discharge of cornu ammonis 3 pyramidal cells. Although during the first postnatal week, sharp-wave events are associated with hippocampal unit bursts in the pyramidal layer, ripple oscillations are absent. We investigated the emergence of fast-field oscillations in rat pups ranging from postnatal day 12-20 by recording with wire tetrodes in freely behaving pups and with 16-site linear silicon probes in head fixed animals. Cornu ammonis 1 pyramidal cell layer was determined by the presence of multiple unit activity and a reversal of the field potential in the deeper electrode sites. On-line verification of the recording sites was determined via an evoked response to commissural stimulation, showing a clear reversal in the field potential. Sharp wave-associated fast-field oscillations did not begin to emerge until the end of the second postnatal week and showed a gradual increase until day 18. Once ripples emerged, the intra-ripple frequency assumed adult values. The developmental time course of the ripple parallels the switch in the GABA(A) receptor-mediated signaling from excitation to inhibition. The time course may also reflect hitherto unidentified emergence of neuronal gap junctions.

Age Factors↗
PubMed2004

Capillary level imaging of local cerebral blood flow in bicuculline-induced epileptic foci.

Local hemodynamics of the cerebral cortex is the basis of modern functional imaging techniques, such as fMRIand PET. Despite the importance of local regulation of the blood flow, capillary level quantification of cerebral blood flow has been limited by the spatial resolution of functional imaging techniques and the depth penetration of conventional optical microscopy. Two-photon laser scanning microscopic imaging technique has the necessary spatial resolution and can image capillaries in the depth of the cortex. We have loaded the serum with fluorescein isothiocyanate dextran and quantified the flow of red blood cells (RBCs) in capillaries in layers 2/3 of the mouse somatosensory cortex in vivo. Basal capillary flux was quantified as approximately 28.9+/-13.6 RBCs/s (n=50, mean+/-S.D.) under ketamine-xylazine anesthesia and 26.7+/-16.0 RBCs/s (n=31) under urethane anesthesia. Focal interictal (epileptiform) activity was induced by local infusion of bicuculline methochloride in the cortex. We have observed that capillary blood flow increased as the cortical local field events developed into epileptiform in the vicinity of GABA receptor blockade (<300 microm from the administration site). Local blood flow in the interictal focus increased significantly (42.5+/-18.5RBCs/s, n=52) relative to the control conditions or to blood flow measured in capillaries at distant (>1mm from the focus) sites from the epileptic focus (27.8+/-12.9 RBCs/s, n=30). These results show that hyper-synchronized neural activity is associated with increased capillary perfusion in a localized cortical area. This volume is significantly smaller than the currently available resolution of the fMRI signal.

Animals↗
PubMed2003

Hippocampal network patterns of activity in the mouse.

Genetic engineering of the mouse brain allows investigators to address novel hypotheses in vivo. Because of the paucity of information on the network patterns of the mouse hippocampus, we investigated the electrical patterns in the behaving animal using multisite silicon probes and wire tetrodes. Theta (6-9 Hz) and gamma (40-100 Hz) oscillations were present during exploration and rapid eye movement sleep. Gamma power and theta power were comodulated and gamma power varied as a function of the theta cycle. Pyramidal cells and putative interneurons were phase-locked to theta oscillations. During immobility, consummatory behaviors and slow-wave sleep, sharp waves were present in cornu ammonis region CA1 of the hippocampus stratum radiatum associated with 140-200-Hz "ripples" in the pyramidal cell layer and population burst of CA1 neurons. In the hilus, large-amplitude "dentate spikes" occurred in association with increased discharge of hilar neurons. The amplitude of field patterns was larger in the mouse than in the rat, likely reflecting the higher neuron density in a smaller brain. We suggest that the main hippocampal network patterns are mediated by similar pathways and mechanisms in mouse and rat.

Animals↗
PubMed2001

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells.

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.

Action Potentials↗
PubMed2001

Electrical wiring of the oscillating brain.

In this issue of Neuron, two laboratories (Deans et al. and Hormuzdi et al.) find that cortical gamma oscillation in vitro is impaired in the Cx36 knockout mouse. What are the implications?

Animals↗
PubMed2001

Firing rates of hippocampal neurons are preserved during subsequent sleep episodes and modified by novel awake experience.

What determines the firing rate of cortical neurons in the absence of external sensory input or motor behavior, such as during sleep? Here we report that, in a familiar environment, the discharge frequency of simultaneously recorded individual CA1 pyramidal neurons and the coactivation of cell pairs remain highly correlated across sleep-wake-sleep sequences. However, both measures were affected when new sets of neurons were activated in a novel environment. Nevertheless, the grand mean firing rate of the whole pyramidal cell population remained constant across behavioral states and testing conditions. The findings suggest that long-term firing patterns of single cells can be modified by experience. We hypothesize that increased firing rates of recently used neurons are associated with a concomitant decrease in the discharge activity of the remaining population, leaving the mean excitability of the hippocampal network unaltered.

Animals↗
PubMed2001

Behavior-dependent states of the hippocampal network affect functional clustering of neurons.

Local versus distant coherence of hippocampal CA1 pyramidal cells was investigated in the behaving rat. Temporal cross-correlation of pyramidal cells revealed a significantly stronger relationship among local (<140 microm) pyramidal neurons compared with distant (>300 microm) neurons during non-theta-associated immobility and sleep but not during theta-associated running and walking. In contrast, cross-correlation between local pyramidal cell-interneuron pairs was significantly stronger than between distant pairs during theta oscillations but were similar during non-theta-associated behaviors. We suggest that network state-dependent functional clustering of neuronal activity emerges because of the differential contribution of the main excitatory inputs, the perforant path, and Schaffer collaterals during theta and non-theta behaviors.

Action Potentials↗
PubMed2001

The apical shaft of CA1 pyramidal cells is under GABAergic interneuronal control.

Dendrites of pyramidal cells perform complex amplification and integration (reviewed in Refs 5, 9, 12 and 20). The presence of a large proximal apical dendrite has been shown to have functional implications for neuronal firing patterns (13) and under a variety of experimental conditions, the largest increases in intracellular Ca2+ occur in the apical shaft.(4,8,15,16,19,21-23) An important step in understanding the functional role of the proximal apical dendrite is to describe the nature of synaptic input to this dendritic region. Using light and electron microscopic methods combined with in vivo labeling of rat hippocampal CA1 pyramidal cells, we examined the total number of GABAergic and non-GABAergic inputs converging onto the first 200microm of the apical trunk. The number of spines associated with excitatory terminals increased from <0.2 spines/microm adjacent to the soma to 5.5 spines/microm at 200microm from the soma, whereas the number of GABAergic, symmetric terminals decreased from 0.8/microm to 0.08/microm over the same anatomical region. GABAergic terminals were either parvalbumin-, cholecystokinin- or vasointestinal peptide-immunoreactive. These findings indicate that the apical dendritic trunk mainly receives synaptic input from GABAergic interneurons. GABAergic inhibition during network oscillation may serve to periodically isolate the dendritic compartments from the perisomatic action potential generating sites.

Animals↗
PubMed2001

Action potential threshold of hippocampal pyramidal cells in vivo is increased by recent spiking activity.

Understanding the mechanisms that influence the initiation of action potentials in single neurons is an important step in determining the way information is processed by neural networks. Therefore, we have investigated the properties of action potential thresholds for hippocampal neurons using in vivo intracellular recording methods in Sprague-Dawley rats. The use of in vivo recording has the advantage of the presence of naturally occurring spatio-temporal patterns of synaptic activity which lead to action potential initiation. We have found there is a large variability in the threshold voltage (5.7+/-1.7 mV; n=22) of individual action potentials. We have identified two separate factors that contribute to this variation in threshold: (1) fast rates of membrane potential change prior to the action potential are associated with more hyperpolarized thresholds (increased excitability) and (2) the occurrence of other action potentials in the 1 s prior to any given action potential is associated with more depolarized thresholds (decreased excitability). We suggest that prior action potentials cause sodium channel inactivation that recovers with approximately a 1-s time constant and thus depresses action potential threshold during this period.

Action Potentials↗
PubMed2001

Hippocampal GABAergic interneurons: a physiological perspective.

Oscillations within and across neuronal systems are believed to serve various complex functions, such as perception, cognition, movement initiation, plasticity and memory. GABAergic interneurons and their inhibitory synapses play a major role in these oscillatory patterns. Networks of inhibitory interneurons impose a coordinated oscillatory "context" for the "content" carried by networks of principal cells. This hypothesis implies that GABAergic neuronal "supernetworks" may cooperatively entrain large populations of pyramidal cells throughout the forebrain. Experiments on hippocampal interneurons are reviewed and possible solutions for some of these complex functions are illustrated.

Hippocampus↗
PubMed2000

Unusual target selectivity of perisomatic inhibitory cells in the hilar region of the rat hippocampus.

Perisomatic inhibitory innervation of all neuron types profoundly affects their firing characteristics and vulnerability. In this study we examined the postsynaptic targets of perisomatic inhibitory cells in the hilar region of the dentate gyrus where the proportion of potential target cells (excitatory mossy cells and inhibitory interneurons) is approximately equal. Both cholecystokinin (CCK)- and parvalbumin-immunoreactive basket cells formed multiple contacts on the somata and proximal dendrites of mossy cells. Unexpectedly, however, perisomatic inhibitory terminals arriving from these cell types largely ignored hilar GABAergic cell populations. Eighty-ninety percent of various GABAergic neurons including other CCK-containing basket cells received no input from CCK-positive terminals. Parvalbumin-containing cells sometimes innervated each other but avoided 75% of other GABAergic cells. Overall, a single mossy cell received 40 times more CCK-immunoreactive terminals and 15 times more parvalbumin-positive terminals onto its soma than the cell body of an average hilar GABAergic cell. In contrast to the pronounced target selectivity in the hilar region, CCK- and parvalbumin-positive neurons innervated each other via collaterals in stratum granulosum and moleculare. Our observations indicate that the inhibitory control in the hilar region is qualitatively different from other cortical areas at both the network level and the level of single neurons. The paucity of perisomatic innervation of hilar interneurons should have profound consequences on their action potential generation and on their ensemble behavior. These findings may help explain the unique physiological patterns observed in the hilus and the selective vulnerability of the hilar cell population in various pathophysiological conditions.

Animals↗
PubMed2000

Multiple site silicon-based probes for chronic recordings in freely moving rats: implantation, recording and histological verification.

This paper describes the procedure of assembling a miniature microdrive and silicon probe system for surgical implantation into the adult rat brain. Successful recordings of single and multiunit activity with parallel depth profiles of spontaneous and evoked field potentials are shown. The procedure for histological verification of the position of the silicon probe is described.

Age Factors↗
PubMed2000

Physiological patterns in the hippocampo-entorhinal cortex system.

The anatomical connectivity and intrinsic properties of entorhinal cortical neurons give rise to ordered patterns of ensemble activity. How entorhinal ensembles form, interact, and accomplish emergent processes such as memory formation is not well-understood. We lack sufficient understanding of how neuronal ensembles in general can function transiently and distinctively from other neuronal ensembles. Ensemble interactions are bound, foremost, by anatomical connectivity and temporal constraints on neuronal discharge. We present an overview of the structure of neuronal interactions within the entorhinal cortex and the rest of the hippocampal formation. We wish to highlight two principle features of entorhinal-hippocampal interactions. First, large numbers of entorhinal neurons are organized into at least two distinct high-frequency population patterns: gamma (40-100 Hz) frequency volleys and ripple (140-200 Hz) frequency volleys. These patterns occur coincident with other well-defined electrophysiological patterns. Gamma frequency volleys are modulated by the theta cycle. Ripple frequency volleys occur on each sharp wave event. Second, these patterns occur dominantly in specific layers of the entorhinal cortex. Theta/gamma frequency volleys are the principle pattern observed in layers I-III, in the neurons that receive cortical inputs and project to the hippocampus. Ripple frequency volleys are the principle population pattern observed in layers V-VI, in the neurons that receive hippocampal output and project primarily to the neocortex. Further, we will highlight how these ensemble patterns organize interactions within distributed forebrain structures and support memory formation.

Afferent Pathways↗
PubMed2000

Ensemble patterns of hippocampal CA3-CA1 neurons during sharp wave-associated population events.

Transfer of neuronal patterns from the CA3 to CA1 region was studied by simultaneous recording of neuronal ensembles in the behaving rat. A nonlinear interaction among pyramidal neurons was observed during sharp wave (SPW)-related population bursts, with stronger synchrony associated with more widespread spatial coherence. SPW bursts emerged in the CA3a-b subregions and spread to CA3c before invading the CA1 area. Synchronous discharge of >10% of the CA3 within a 100 ms window was required to exert a detectable influence on CA1 pyramidal cells. Activity of some CA3 pyramidal neurons differentially predicted the ripple-related discharge of circumscribed groups of CA1 pyramidal cells. We suggest that, in SPW behavioral state, the coherent discharge of a small group of CA3 cells is the primary cause of spiking activity in CA1 pyramidal neurons.

Action Potentials↗
PubMed2000

Two-phase computational model training long-term memories in the entorhinal-hippocampal region.

The computational model described here is driven by the hypothesis that a major function of the entorhinal cortex (EC)-hippocampal system is to alter synaptic connections in the neocortex. It is based on the following postulates: (1) The EC compares the difference between neocortical representations (primary input) and feedback information conveyed by the hippocampus (the "reconstructed input"). The difference between the primary input and the reconstructed input (termed "error") initiates plastic changes in the hippocampal networks (error compensation). (2) Comparison of the primary input and reconstructed input requires that these representations are available simultaneously in the EC network. We suggest that compensation of time delays is achieved by predictive structures, such as the CA3 recurrent network and EC-CA1 connections. (3) Alteration of intrahippocampal connections gives rise to a new hippocampal output. The hippocampus generates separated (independent) outputs, which, in turn, train long-term memory traces in the EC (independent components, IC). The ICs of the long-term memory trace are generated in a two-step manner, the operations of which we attribute to the activities of the CA3 (whitening) and CA1 (separation) fields. (4) The different hippocampal fields can perform both nonlinear and linear operations, albeit at different times (theta and sharp phases). We suggest that long-term memory is represented in a distributed and hierarchical reconstruction network, which is under the supervision of the hippocampal output. Several of these model predictions can be tested experimentally.

Computer Simulation↗
PubMed2000

Intracellular features predicted by extracellular recordings in the hippocampus in vivo.

Multichannel tetrode array recording in awake behaving animals provides a powerful method to record the activity of large numbers of neurons. The power of this method could be extended if further information concerning the intracellular state of the neurons could be extracted from the extracellularly recorded signals. Toward this end, we have simultaneously recorded intracellular and extracellular signals from hippocampal CA1 pyramidal cells and interneurons in the anesthetized rat. We found that several intracellular parameters can be deduced from extracellular spike waveforms. The width of the intracellular action potential is defined precisely by distinct points on the extracellular spike. Amplitude changes of the intracellular action potential are reflected by changes in the amplitude of the initial negative phase of the extracellular spike, and these amplitude changes are dependent on the state of the network. In addition, intracellular recordings from dendrites with simultaneous extracellular recordings from the soma indicate that, on average, action potentials are initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s. Finally we determined that a tetrode in hippocampal area CA1 theoretically should be able to record electrical signals from approximately 1, 000 neurons. Of these, 60-100 neurons should generate spikes of sufficient amplitude to be detectable from the noise and to allow for their separation using current spatial clustering methods. This theoretical maximum is in contrast to the approximately six units that are usually detected per tetrode. From this, we conclude that a large percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral condition.

Action Potentials↗