Hippocampo-cerebellar theta band phase synchrony in rabbits.

Hippocampal functioning, in the form of theta band oscillation, has been shown to modulate and predict cerebellar learning of which rabbit eyeblink conditioning is perhaps the most well-known example. The contribution of hippocampal neural activity to cerebellar learning is only possible if there is a functional connection between the two structures. Here, in the context of trace eyeblink conditioning, we show (1) that, in addition to the hippocampus, prominent theta oscillation also occurs in the cerebellum, and (2) that cerebellar theta oscillation is synchronized with that in the hippocampus. Further, the degree of phase synchrony (PS) increased both as a response to the conditioning stimuli and as a function of the relative power of hippocampal theta oscillation. However, the degree of PS did not change as a function of either training or learning nor did it predict learning rate as the hippocampal theta ratio did. Nevertheless, theta band synchronization might reflect the formation of transient neural assemblies between the hippocampus and the cerebellum. These findings help us understand how hippocampal function can affect eyeblink conditioning, during which the critical plasticity occurs in the cerebellum. Future studies should examine cerebellar unit activity in relation to hippocampal theta oscillations in order to discover the detailed mechanisms of theta-paced neural activity.

Frequency bands and spatiotemporal dynamics of beta burst stimulation induced afterdischarges in hippocampus in vivo.

Temporal and spatial characteristics of hippocampal neuronal network activation are modified during epileptiform afterdischarges. We developed a beta burst stimulation protocol to investigate subregional variations and substrates of rhythmic population spike discharges in vivo in urethane anesthetized Wistar rat hippocampus with a 14-electrode recording array and extracellular single electrode recordings. Our 64 pulse beta burst stimulation protocol was constructed from electrical pulses delivered at intervals corresponding to beta (14-25 Hz), Delta (2 Hz), and slow (0.5 Hz) frequencies. In each experiment these interleaved pulses were all repeated four times with unchanged intervals. Stimulation of either perforant path or fimbria fornix induced a prolonged afterdischarge pattern peaking at 200 Hz fast, 20 Hz beta, and 2 Hz Delta frequencies. Analysis of variance confirmed that the response pattern of the discharges remained constant regardless of the stimulation beta frequency. Within the afterdischarge the fast frequencies were restricted to independent hippocampal subfields whereas beta and slow frequencies correlated across the subfields. Current source density (CSD) analysis revealed that the original signal propagation through subfields of the hippocampus was compromised during the beta burst stimulation induced afterdischarge. In addition, the CSD profile of the epileptiform afterdischarge was consistently similar across the different experiments. Time-frequency analysis revealed that the beta frequency afterdischarge was initiated and terminated at higher gamma (30-80 Hz) frequencies. However, the alterations in the CSD profile of the hippocampus coincided with the beta frequency dominated discharges. We propose that hippocampal epileptiform activity at fast, beta and Delta frequencies represents coupled oscillators at respectively increasing spatial scales in the hippocampal neuronal network in vivo.

Electrophysiologic changes in the lateral and basal amygdaloid nuclei in temporal lobe epilepsy: an in vitro study in epileptic rats.

The functional consequences of neuronal loss during epileptogenesis in the lateral and basal amygdaloid nuclei are poorly understood. The present study tested the hypothesis that electrical responsiveness varies in different amygdaloid nuclei in the chronically epileptic amygdala. Further, we examined the amygdaloid region most prone to seizure initiation. Epileptogenesis was triggered in 20 rats by inducing status epilepticus (SE) with electrical stimulation of the lateral nucleus of the amygdala. Electrode-implanted non-stimulated rats served as controls. The occurrence and duration of spontaneous seizures were monitored with video-electroencephalography (EEG) at 8-9 weeks after SE. Thereafter, animals were killed and extracellular recordings were made from slices of both amygdalas. In the lateral nucleus of epileptic animals, the frequency of spontaneous responses was reduced compared with controls (P < 0.05). The amplitudes of evoked field responses were reduced (P < 0.01), whereas paired pulse (PP) facilitation was enhanced (P < or = 0.05). In the basal nucleus of the epileptic animals, PP facilitation was enhanced (P < 0.05) and sensitivity to 4-aminopyridine (4-AP)-induced epileptiform activity was increased compared with controls (P < 0.05). In the epileptic animals, the basal nucleus was also more sensitive than the lateral nucleus to 4-AP-induced epileptiform activity (P < 0.05). Correlation analysis indicated that longer SE duration was associated with longer half widths (P = 0.001) and smaller slopes (P < 0.05) of evoked responses as well as with attenuated PP facilitation (P<0.01). Moreover, a higher frequency of spontaneous seizures was associated with longer half widths (P < 0.05) and smaller slopes (P < 0.05) of evoked responses as well as with enhanced PP facilitation (P < 0.05). These data suggest that there is a reduced release of glutamate and reduced inhibition in the lateral and basal amygdaloid nuclei in epileptic animals. Further, the basal nucleus is more prone to epileptic activity than the lateral nucleus. Finally, the severity of SE and spontaneous seizures in vivo is associated with electrophysiologic alterations in vitro.

Hippocampus retains the periodicity of gamma stimulation in vivo.

Several behavioral state dependent oscillatory rhythms have been identified in the brain. Of these neuronal rhythms, gamma (20-70 Hz) oscillations are prominent in the activated brain and are associated with various behavioral functions ranging from sensory binding to memory. Hippocampal gamma oscillations represent a widely studied band of frequencies co-occurring with information acquisition. However, induction of specific gamma frequencies within the hippocampal neuronal network has not been satisfactorily established. Using both in vivo intracellular and extracellular recordings from anesthetized rats, we show that hippocampal CA1 pyramidal cells can discharge at frequencies determined by the preceding gamma stimulation, provided that the gamma is introduced in theta cycles, as occurs in vivo. The dynamic short-term alterations in the oscillatory discharge described in this paper may serve as a coding mechanism in cortical neuronal networks.

Cerebral T1rho relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization.

Time-dependent changes of T1 in the rotating frame (T1rho), diffusion, T2, and magnetization transfer contrast on cardiac arrest-induced global ischemia in rat were investigated. T1rho, as acquired with spin lock amplitudes >0.6 G, started to increase 10-20 sec after cardiac arrest followed by an increase within 3-4 min to a level that was 6-8% greater than in normal brain. The ischemic T1rho response coincided with the drop of water diffusion coefficient in normoglycemic animals. However, unlike the rate of diffusion, the kinetics of T1rho were not affected by either preischemic hypoglycemia or hyperglycemia. Similar to diffusion, the kinetics of anoxic depolarization were dependent on preischemic blood glucose levels. Ischemia caused a reduction in the Hahn spin echo T2 as a result of blood oxygenation level-dependent (BOLD) effect; maximal negative BOLD seen by 40 sec. In the animals injected with an ironoxide particle contrast agent, AMI-227, prior to the insult, both T1rho and T2 immediately increased in concert on induction of ischemia. In contrast to the T1rho and diffusion changes, a much slower change in magnetization transfer contrast was evident over the first 20 min of ischemia. These data demonstrate that T1rho immediately increases following ischemia and that the pathophysiological mechanisms affecting this relaxation time may not directly involve magnetization transfer. The mechanisms prolonging T1rho differ from those affecting water diffusion with respect to their sensitivities to glucose and are apparently independent of membrane depolarization.

Use of spin echo T(2) BOLD in assessment of cerebral misery perfusion at 1.5 T.

Inadequate blood supply relative to metabolic demand, a haemodynamic condition termed as misery perfusion, often occurs in conjunction with acute ischaemic stroke. Misery perfusion results in adaptive changes in cerebral physiology including increased cerebral blood volume (CBV) and oxygen extraction ratio (OER) to secure substrate supply for the brain. It has been suggested that the presence of misery perfusion may be an indication of reversible ischaemia, thus detection of this condition may have clinical impact in acute stroke imaging. The ability of single spin echo T(2) to detect misery perfusion in the rat brain at 1.5 T owing to its sensitivity to blood oxygenation level dependent (BOLD) contrast was studied both theoretically and experimentally. Based on the known physiology of misery perfusion, tissue morphometry and blood relaxation data, T(2) behaviour in misery perfusion was simulated. The interpretation of these computations was experimentally assessed by quantifying T(2) in a rat model for cerebral misery perfusion. CBF was quantified with the H(2) clearance method. A drop of CBF from 58+/-8 to 17+/-3 ml/100 g/min in the parieto-frontal cortex caused shortening of T(2) from 66.9+/-0.4 to 64.6+/-0.5 ms. Under these conditions, no change in diffusion MRI was detected. In contrast, the cortex with CBF of 42+/-7 ml/100 g/min showed no change in T(2). Computer simulations accurately predicted these T(2) responses. The present study shows that the acute drop of CBF by 70% causes a negative BOLD that is readily detectable by T(2) MRI at 1.5 T. Thus BOLD may serve as an index of misery perfusion thus revealing viable tissue with increased OER.

Early detection of irreversible cerebral ischemia in the rat using dispersion of the magnetic resonance imaging relaxation time, T1rho.

The impact of brain imaging on the assessment of tissue status is likely to increase with the advent of treatment methods for acute cerebral ischemia. Multimodal magnetic resonance imaging (MRI) demonstrates potential for selecting stroke therapy patients by identifying the presence of acute ischemia, delineating the perfusion defect, and excluding hemorrhage. Yet, the identification of tissue subject to reversible or irreversible ischemia has proven to be difficult. Here, the authors show that T1 relaxation time in the rotating frame, so-called T1rho, serves as a sensitive MRI indicator of cerebral ischemia in the rat. The T1rho prolongs within minutes after a drop in the CBF of less than 22 mL 100 g(-1) min(-1). Dependence of T1rho on spin-lock amplitude, termed as T1rho dispersion, increases by approximately 20% on middle cerebral artery (MCA) occlusion, comparable with the magnitude of diffusion reduction. The T1rho dispersion change dynamically increases to be 38% +/- 10% by the first 60 minutes of ischemia in the brain region destined to develop infarction. Following reperfusion after 45 minutes of MCA occlusion, the tissue with elevated T1rho dispersion (yet normal diffusion) develops severe histologically verified neuronal damage; thus, the former parameter unveils an irreversible condition earlier than currently available MRI methods. The T1rho dispersion as a novel MRI index of cerebral ischemia may be useful in determination of the therapeutic window for acute ischemic stroke.

Graded reduction of cerebral blood flow in rat as detected by the nuclear magnetic resonance relaxation time T2: a theoretical and experimental approach.

The ability of transverse nuclear magnetic resonance relaxation time, T2, to reveal acutely reduced CBF was assessed using magnetic resonance imaging (MRI). Graded reduction of CBF was produced in rats using a modification of Pulsinelli's four-vessel occlusion model. The CBF in cerebral cortex was quantified using the hydrogen clearance method, and both T2 and the trace of the diffusion tensor (Dav = 1/3TraceD) in the adjacent cortical tissue were determined as a function of reduced CBF at 4.7 T. A previously published theory, interrelating cerebral hemodynamic parameters, hemoglobin, and oxygen metabolism with T2, was used to estimate the effects of reduced CBF on cerebral T2. The MRI data show that T2 reduces in a U-shape manner as a function of CBF, reaching a level that is 2.5 to 2.8 milliseconds (5% to 6%) below the control value at CBF, between 15% and 60% of normal. This reduction could be estimated by the theory using the literature values of cerebral blood volume, oxygen extraction ratio, and precapillary oxygen extraction during compromised CBF. Dav dropped with two apparent flow thresholds, so that a small 11% to 17% reduction occurred between CBF values of 16% to 45% of normal, followed by a precipitous collapse by more than 20% at CBF below 15% of normal. The current data show that T2 can be used as an indicator of acute hypoperfusion because of its ability to indicate blood oxygenation level-dependent phenomena on reduced CBF.

Ultra-slow oscillation (0.025 Hz) triggers hippocampal afterdischarges in Wistar rats.

Oscillations in neuronal networks are assumed to serve various physiological functions, from coordination of motor patterns to perceptual binding of sensory information. Here, we describe an ultra-slow oscillation (0.025 Hz) in the hippocampus. Extracellular and intracellular activity was recorded from the CA1 and subicular regions in rats of the Wistar and Sprague-Dawley strains, anesthetized with urethane. In a subgroup of Wistar rats (23%), spontaneous afterdischarges (4.7+/-1.6 s) occurred regularly at 40.8+/-15.7 s. The afterdischarge was initiated by a fast increase of population synchrony (100-250 Hz oscillation; "tonic" phase), followed by large-amplitude rhythmic waves and associated action potentials at gamma and beta frequency (15-50 Hz; "clonic" phase). The afterdischarges were bilaterally synchronous and terminated relatively abruptly without post-ictal depression. Single-pulse stimulation of the commissural input could trigger afterdischarges, but only at times when they were about to occur. Commissural stimulation evoked inhibitory postsynaptic potentials in pyramidal cells. However, when the stimulus triggered an afterdischarge, the inhibitory postsynaptic potential was absent and the cells remained depolarized during most of the afterdischarge. Afterdischarges were not observed in the Sprague-Dawley rats. Long-term analysis of interneuronal activity in intact, drug-free rats also revealed periodic excitability changes in the hippocampal network at 0.025 Hz. These findings indicate the presence of an ultra-slow oscillation in the hippocampal formation. The ultra-slow clock induced afterdischarges in susceptible animals. We hypothesize that a transient failure of GABAergic inhibition in a subset of Wistar rats is responsible for the emergence of epileptiform patterns.

Gamma frequency oscillation in the hippocampus of the rat: intracellular analysis in vivo.

Gamma frequency field oscillations reflect synchronized synaptic potentials in neuronal populations within the approximately 10-40 ms range. The generation of gamma activity in the hippocampus was investigated by intracellular recording from principal cells and basket cells in urethane anaesthetized rats. The recorded neurones were verified by intracellular injection of biocytin. Gamma frequency field oscillations were nested within the slower theta waves. The phase and amplitude of intracellular gamma were voltage dependent with an almost complete phase reversal at Cl- equilibrium potential in pyramidal cells. Basket cells fired at gamma frequency and were phase-locked to the same phase of the gamma oscillation as pyramidal cells. Current-induced depolarization coupled with synaptically induced inhibition resulted in gamma frequency discharge (30-80 Hz) of pyramidal cells without accommodation. These observations suggest that at least part of the gamma frequency field oscillation reflects rhythmic hyperpolarization of principal cells, brought about by the rhythmically discharging basket neurones. Resonant properties of pyramidal cells might facilitate network synchrony in the gamma frequency range.

Auditory cortical event-related potentials to pitch deviances in rats.

We recorded epidural event-related potentials (ERPs) from the auditory cortex in anesthetized rats when pitch-deviant tones were presented in a homogeneous series of standard tones (oddball condition). Additionally, deviant tones were presented without standard tones (deviant-alone condition). ERPs to deviant tones in the oddball condition differed significantly from ERPs to standard tones at the latency range of 63-243 ms. On the other hand, ERPs to deviant tones in the deviant-alone condition did not differ from ERPs to standard tones until 196 ms from stimulus onset. The results suggest that oddball stimuli can be neurophysiologically discriminated in anesthetized rats. Furthermore, as the difference between ERPs to deviant tones and those to standard tones at the 63-196 ms latency range could be detected only when standard tones precede deviant tones it shows concordance with mismatch negativity in humans.

Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: intracellular staining in vivo and in vitro.

Dendritic morphology and passive cable properties determine many aspects of synaptic integration in complex neurons, together with voltage-dependent membrane conductances. We investigated dendritic properties of CA1 pyramidal neurons intracellularly labeled during in vivo and in vitro physiologic recordings, by using similar intracellular staining and three-dimensional reconstruction techniques. Total dendritic length of the in vivo neurons was similar to that of the in vitro cells. After correction for shrinkage, cell extent in three-dimensional representation was not different between the two groups. Both in vivo and in vitro neurons demonstrated a variable degree of symmetry, with some neurons showing more cylindrical symmetry around the main apical axis, whereas other neurons were more elliptical, with the variation likely due to preparation and preservation conditions. Branch order analysis revealed no difference in the number of branch orders or dendritic complexity. Passive conduction of dendritic signals to the soma in these neurons shows considerable attenuation, particularly with higher frequency signals (such as synaptic potentials compared with steady-state signals), despite a relatively short electrotonic length. Essential aspects of morphometric appearance and complex dendritic integration critical to CA1 pyramidal cell functioning are preserved across neurons defined from the two different hippocampal preparations used in this study.

Effects of rewarding electrical stimulation of lateral hypothalamus on classical conditioning of the nictitating membrane response.

1. Adult New Zealand albino rabbits were prepared with chronic hypothalamic stimulating electrodes and hippocampal recording electrodes. 2. Rabbits were restrained and classically conditioned by a tone CS and an airpuff US either followed or preceded by a hypothalamic stimulation (HS). Control rabbits were conditioned without the HS. 3. It was found that HS following the CS facilitated both behavioral and hippocampal responses, while HS preceding the CS inhibited them. 4. Enhanced hippocampal learning-related unit firing to the CS may represent an early indication of conditioning before the behavioral activity produces any observable change.

Termination of epileptic afterdischarge in the hippocampus.

The mechanism of afterdischarge termination in the various hippocampal regions was examined in the rat. Stimulation of the perforant path or the commissural system was used to elicit afterdischarges. Combination of multiple site recordings with silicon probes, current source density analysis, and unit recordings in the awake animal allowed for a high spatial resolution of the field events. Interpretation of the field observations was aided by intracellular recordings from anesthetized rats. Irrespective of the evoking conditions, afterdischarges always terminated first in the CA1 region. Termination of the afterdischarge was heralded by a large DC shift initiated in dendritic layers associated with a low amplitude "afterdischarge termination oscillation" (ATO) at 40 to 80 Hz in the cell body layer. ATOs were also observed in the CA3 region and the dentate gyrus. The DC shift spread at the same velocity (0. 1-0.2 mm/sec) in all directions and could cross the hippocampal fissure. All but 1 of the 25 putative interneurons in the CA1 and dentate regions ceased to fire before the onset of ATO. Intracellularly, ATO and the emerging DC potential were associated with fast depolarizing potentials and firing of pyramidal cells and depolarization block of spike initiation, respectively. Both field ATO and the intracellular depolarization shift were replicated by focal microinjection of potassium. We hypothesize that [K+]o lost by the intensely discharging neurons during the afterdischarge triggers propagating waves of depolarization in the astrocytic network. In turn, astrocytes release potassium, which induces a depolarization block of spike generation in neurons, resulting in "postictal depression" of the EEG.

Interneurons in the hippocampal dentate gyrus: an in vivo intracellular study.

Interneurons in the dentate area were characterized physiologically and filled with biocytin in urethane-anaesthetized rats. On the basis of axonal targets the following groups could be distinguished. (i) Large multipolar interneurons with spiny dendrites in the deep hilar region densely innervated the outer molecular layer and contacted both granule cells and parvalbumin-positive neurons (hilar interneuron with perforant pathway-associated axon terminals; HIPP cells). (ii) A pyramidal-shaped neuron with a cell body located in the subgranular layer innervated mostly the inner molecular layer and the granule cell layer (hilar interneuron with commissural-associational pathway-associated axon terminals; HICAP cell). It contacted both granule cells and interneurons. Axon collaterals of HIPP and HICAP neurons covered virtually the entire septo-temporal extent of the dorsal dentate gyrus. (iii) Calbindin-immunoreactive neurons with horizontal dendrites in stratum oriens of the CA3c region gave rise to a rich axon arbor in strata oriens, pyramidale and radiatum and innervated almost the entire extent of the dorsal hippocampus, with some collaterals entering the subicular area (putative trilaminar cell). (iv) Hilar basket cells innervated mostly the granule cell layer and to some extent the inner molecular layer and the CA3c pyramidal layer. HIPP and trilaminar interneurons could be antidromically activated by stimulation of the fimbria. Only the HICAP cells could be monosynaptically discharged by the perforant path input. All interneurons examined showed phase-locked activity to the extracellularly recorded theta/gamma oscillations or to irregular dentate electroencephalogram spikes. These observations indicate that the interconnected interneuronal system plays a critical role in coordinating population of the dentate gyrus and Ammon's hom.

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.

Feed-forward and feed-back activation of the dentate gyrus in vivo during dentate spikes and sharp wave bursts.

Intermittently occurring field events, dentate spikes (DS), and sharp waves (SPW) in the hippocampus reflect population synchrony of principal cells and interneurons along the entorhinal cortex-hippocampus axis. We have investigated the cellular-synaptic generation of DSs and SPWs by intracellular recording from granule cells, pyramidal cells, and interneurons in anesthetized rats. The recorded neurons were anatomically identified by intracellular injection of biocytin. Extracellular recording electrodes were placed in the hilus to record field DSs and multiple units and in the CA1 pyramidal cell layer to monitor SPW-associated fast field oscillations (ripples) and unit activity. DSs were associated with large depolarizing potentials in granule cells, but they rarely discharged action potentials. When they were depolarized slightly with intracellular current injection, bursts of action potentials occurred concurrently with extracellularly recorded DSs. Two interneurons in the hilar region were also found to discharge preferentially with DSs. In contrast, CA1 pyramidal cells, recorded extracellularly and intracellularly, were suppressed during DSs. In association with field SPWs, extracellular recordings from the CA1 pyramidal layer and the hilar region revealed synchronous bursting of these cell populations. Intracellular recordings from CA3 and CA1 pyramidal cells, granule cells, and from a single CA3 region interneuron revealed SPW-concurrent depolarizing potentials and action potentials. These findings suggest that granule cells may be discharged anterogradely by entorhinal input or retrogradely by the CA3-mossy cell feedback pathway during DSs and SPWs, respectively. Although both of these intermittent population patterns can activate granule cells, the impact of DSs and SPWs is diametrically opposite on the rest of the hippocampal circuitry. Entorhinal cortex activation of the granule cells during DSs induces a transient decrease in the hippocampal output, whereas during SPW bursts every principal cell population of the hippocampal formation may be recruited into the population event.

Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo.

The invasion of sodium spikes from the soma into dendrites was studied in hippocampal pyramidal cells by simultaneous extracellular and intracellular recordings in anesthetized rats and by simultaneous extracellular recordings of the somatic and dendritic potentials in freely behaving animals. During complex-spike patterns, recorded in the immobile or sleeping animal, dendritic invasion of successive spikes was substantially attenuated. Complex-spike bursts occurred in association with population discharge of CA3-CA1 pyramidal cells (sharp wave field events). Synaptic inhibition reduced the amplitude of sodium spikes in the dendrites and prevented the occurrence of calcium spikes. These findings indicate that (i) the voltage-dependent calcium influx into the dendrites is under the control of inhibitory neurons and (ii) the temporal coincidence of synaptic depolarization and activation of voltage-dependent calcium conductances by the backpropagating spikes during sharp wave bursts may be critical for synaptic plasticity in the intact hippocampus.

Hippocampal CA1 interneurons: an in vivo intracellular labeling study.

Fast spiking interneurons in the CA1 area of the dorsal hippocampus were recorded from and filled with biocytin in anesthetized rats. The full extent of their dendrites and axonal arborizations as well as their calcium binding protein content were examined. Based on the spatial extent of axon collaterals, local circuit cells (basket and O-LM neurons) and long-range cells (bistratified, trilaminar, and backprojection neurons) could be distinguished. Basket cells were immunoreactive for parvalbumin and their axon collaterals were confined to the pyramidal layer. A single basket cell contacted more than 1500 pyramidal neurons and 60 other parvalbumin-positive interneurons. Commissural stimulation directly discharged basket cells, followed by an early and late IPSPs, indicating interneuronal inhibition of basket cells. The dendrites of another local circuit neuron (O-LM) were confined to stratum oriens and it had a small but high-density axonal terminal field in stratum lacunosum-moleculare. The fastest firing cell of all interneurons was a calbindin-immunoreactive bistratified neuron with axonal targets in stratum oriens and radiatum. Two neurons with their cell bodies in the alveus innervated the CA3 region (backprojection cells), in addition to rich axon collaterals in the CA1 region. The trilaminar interneuron had axon collaterals in strata radiatum, oriens and pyramidale with its dendrites confined to stratum oriens. Commissural stimulation evoked an early EPSP-IPSP-late depolarizing potential sequence in this cell. All interneurons formed symmetric synapses with their targets at the electron microscopic level. These findings indicate that interneurons with distinct axonal targets have differential functions in shaping the physiological patterns of the CA1 network.

Hippocampal event-related potentials to pitch deviances in an auditory oddball situation in the cat: experiment I.

Hippocampal event-related potentials (ERP) in the areas CA1, CA3, and dentate fascia (Df) were recorded in cats during an oddball situation when pitch deviant tones occurred in a series of standard tones. When difference waves were calculated by subtracting ERPs to the standard tones from those to the deviant tones, no clear N40d, corresponding to a cat analogue of the human mismatch negativity (MMN) observed in earlier studies, could be detected. Instead, a prominent later negativity (N130d) was observed. A possible extra-hippocampal source of the process reflected by the MMN-like negativity, and a relation between an orienting response (OR) and the N130d are discussed.