CA3 Network Research Articles

海馬ＣＡ１野の入力と出力逆伝搬の時間タイミング依存性ＬＴＰ／ＬＴＤ

Spatial distributions of LTP/LTD were investigated in the CA1 area of hippocampal slices by optical imaging method. A pair of electrical pulse stimuli was used to stimulate the schaffer collateral (Stim. A) and the stratum oriens (Stim. B) with various sets of the relative timing (τ). LTP was induced with -10ms<τ<10ms, τ=0ms led to the widest and strongest LTP. On the other hand, τ=±20ms induced LTD. In particular, this LTD at τ=20ms was something that had not been observed by others using cultured hippocampal neurons. The LTD at τ=20ms was blocked by bicuculline (GABA (gamma-aminobutyric acid) receptor antagonist). The importance of precise spike timing in hippocampal CA1 network is discussed in the light of computational neuroscience involving the covariance learning rule.

Short- and long-term changes in CA1 network excitability after kainate treatment in rats.

Neuron loss, axon sprouting, and the formation of new synaptic circuits have been hypothesized to contribute to seizures in temporal lobe epilepsy (TLE). Using the kainate-treated rat, we examined how alterations in the density of CA1 pyramidal cells and interneurons, and subsequent sprouting of CA1 pyramidal cell axons, were temporally associated with functional changes in the network properties of the CA1 area. Control rats were compared with animals during the first week after kainate treatment versus several weeks after treatment. The density of CA1 pyramidal cells and putative inhibitory neurons in stratum oriens was reduced within 8 days after kainate treatment. Axon branching of CA1 pyramidal cells was similar between controls and animals examined in the first week after kainate treatment but was increased several weeks after kainate treatment. Stimulation of afferent fibers in brain slices containing the isolated CA1 region produced graded responses in slices from controls and kainate-treated rats tested <8 days after treatment. In contrast, synchronous all-or-none bursts of spikes at low stimulus intensity (i.e., "network bursts") were only observed in the CA1 several weeks after kainate treatment. In the presence of bicuculline, the duration of evoked bursts was significantly longer in CA1 pyramidal cells weeks after kainate treatment than from controls or those examined in the first week posttreatment. Spontaneous network bursts were also observed in the isolated CA1 several weeks after kainate treatment in bicuculline-treated slices. The data suggest that the early loss of neurons directly associated with kainate-induced status epilepticus is followed by increased axon sprouting and new recurrent excitatory circuits in CA1 pyramidal cells. These changes characterize the transition from the initial acute effects of the kainate-induced insult to the eventual development of all-or-none epileptiform discharges in the CA1 area.

Dynamics of a hybrid system of a brain neural network and an artificial nonlinear oscillator

In the brain, many functional modules interact with each other to execute complex information processing. Understanding the nature of these interactions is necessary for understanding how the brain functions. In this study, to mimic interacting modules in the brain, we constructed a hybrid system mutually coupling a hippocampal CA3 network as an actual brain module and a radial isochron clock (RIC) simulated by a personal computer as an artificial module. Return map analysis of the CA3-RIC system's dynamics showed the mutual entrainment and complex dynamics dependent on the coupling modes. The phase response curve of CA3 was modeled regarding the CA3 as a nonlinear oscillator. Using the phase response curves of CA3 and RIC, we reconstructed return maps of the hybrid system's dynamics. Although the reconstructed return maps almost agreed with the experimental data, there were deviations dependent on the coupling mode. In particular, we noted that the deviation was smaller under the bidirectional coupling conditions than during the one-way coupling from RIC to CA3. These results suggest that brain modules may flexibly change their dynamical properties through interaction with other modules.

Chaotic stimulus dependent long-term potentiation in the hippocampal CA1 area

In our previous report [Tsukada, M., Aihara, T., Saito, H., Kato, H., 1996. Neural Netw. 9, 1357–1365], the temporal pattern sensitivity of long-term potentiation (LTP) in hippocampal CA1 neurons was estimated by using Markov chain stimuli (MS) with different values of the serial correlation coefficient ρ 1 between successive interstimulus-intervals. In this paper, the effect of chaotic stimuli (CS) on induction of LTP in the hippocampal CA1 area was investigated in comparison with that of MS and periodic pattern stimuli (PS). The CS were produced by a modified Bernoulli map, so that interstimulus sequences with various values of ρ 1 can be generated by changing the parameter B. These stimuli had an identical first order statistics (mean interstimulus-interval), but their higher order statistics such as the serial correlation coefficients were different. The LTP induced by CS at B=2 was significantly larger in magnitude than that of PS and MS, and also depended on the initial value of CS at B=2 and 3. These results suggest that chaotic signals play an important role for memory coding in the hippocampal CA1 network.

Coincident activation of mGluRs and mAChRs imposes theta frequency patterning on synchronised network activity in the hippocampal CA3 region

Activation of metabotropic glutamate receptors (mGluRs) with the broad spectrum mGluR agonist 1S,3R ACPD (10–50 μM) induced spontaneous field potentials at low frequencies (‘burst-mode’ activity; <1 Hz) in the CA3 region of rat hippocampal slices. At higher concentrations (100–400 μM) ACPD switched this form of activity to a second, more complex pattern of activity in which intermittent episodes of theta frequency oscillations predominated (‘theta-mode’ activity; 4–14 Hz). Both patterns of activity were evoked by selective activation of group I mGluRs and, in particular, could be induced by activation of mGluR5 alone using the subtype selective agonist CHPG (0.5–5 mM). In contrast, activation of group II mGluRs (DCG IV; 100 μM) produced only burst-mode behaviour whilst activation of group III mGluRs (L-AP4; 100 μM) did not result in synchronised network activity. Concurrent extra- and intracellular recordings demonstrated that this mGluR-induced theta-mode activity represented the synchronous firing of CA3 pyramidal cells and that it shared a similar temporal signature to that generated by activation of muscarinic acetylcholine receptors (mAChRs). Furthermore, application of mGluR and mAChR agonists at concentrations sufficient to produce only burst-mode activity when applied individually, produced theta-mode activity when co-applied. These data suggest that the level of activation of different mGluRs and mAChRs crucially determine the pattern of rhythmical network activity generated in the hippocampal CA3 network. These results also indicate that individual receptor subtypes (i.e. mGluR5) can initiate patterns of coherent network activity but that interactions between the cholinergic and glutamatergic transmitter systems may also be important factors in governing the temporal patterning of hippocampal network activity.

Granule-Like Neurons at the Hilar/CA3 Border after Status Epilepticus and Their Synchrony with Area CA3 Pyramidal Cells: Functional Implications of Seizure-Induced Neurogenesis

A group of neurons with the characteristics of dentate gyrus granule cells was found at the hilar/CA3 border several weeks after pilocarpine- or kainic acid-induced status epilepticus. Intracellular recordings from pilocarpine-treated rats showed that these "granule-like" neurons were similar to normal granule cells (i. e., those in the granule cell layer) in membrane properties, firing behavior, morphology, and their mossy fiber axon. However, in contrast to normal granule cells, they were synchronized with spontaneous, rhythmic bursts of area CA3 pyramidal cells that survived status epilepticus. Saline-treated controls lacked the population of granule-like cells at the hilar/CA3 border and CA3 bursts. In rats that were injected after status epilepticus with bromodeoxyuridine (BrdU) to label newly born cells, and also labeled for calbindin D(28K) (because it normally stains granule cells), many double-labeled neurons were located at the hilar/CA3 border. Many BrdU-labeled cells at the hilar/CA3 border also were double-labeled with a neuronal marker (NeuN). Taken together with the recent evidence that granule cells that are born after seizures can migrate into the hilus, the results suggest that some newly born granule cells migrate as far as the CA3 cell layer, where they become integrated abnormally into the CA3 network, yet they retain granule cell intrinsic properties. The results provide insight into the physiological properties of newly born granule cells in the adult brain and suggest that relatively rigid developmental programs set the membrane properties of newly born cells, but substantial plasticity is present to influence their place in pre-existing circuitry.

A comparison of context-dependent hippocampal place codes in 1-layer and 2-layer recurrent networks

Recently, it has been suggested that attractor networks may provide a mechanism for context-dependence in hippocampal place codes. We have proposed that context may be coded by “latent attractors” — mutually competitive and internally cooperative cell groups which channel the system's response to afferent stimuli. We have also argued that it is the disynaptically recurrent dentate gyrus–hilus (DGH) system which embodies these latent attractors in the hippocampus. Others have suggested the CA3 network — with its monosynaptic recurrence — is the site. While latent attractors (and, thus, context-dependent coding) can be implemented by a 1-layer or 2-layer recurrent network, we show that a 2-layer recurrent network can implement a sparse context-dependent place-code using latent attractors much more flexibly than a 1-layer network.

Blockade of Neuronal Activity During Hippocampal Development Produces a Chronic Focal Epilepsy in the Rat

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a "critical" period of development, when CA3 networks have a marked propensity to generate electrographic seizures. In an attempt to prevent axonal remodeling, local circuit activity was blocked unilaterally in dorsal hippocampus by continuous infusion of tetrodotoxin (TTX). Field potential recordings from behaving animals were dramatically altered when TTX infusion was initiated at the beginning of the critical period, week 2, but not later in life. Spontaneous, synchronized spikes and electrographic seizures with behavioral accompaniments were observed after 4 weeks of TTX infusion and persisted into adulthood. When recordings were made during TTX infusion, synchronized spiking was recorded in ventral hippocampus as early as 2 weeks after infusate introduction. At this same time, extracellular field recordings from in vitro slices demonstrated spontaneous network-driven "mini-bursts" arising from ventral hippocampal slices. These were abolished by glutamate receptor antagonists. Whole-cell recordings from CA3 neurons revealed bursts of excitatory synaptic potentials coincident with the network bursts recorded extracellularly. Thus, local assemblies of mutually excitatory CA3 pyramidal cells are hyperexcitable in these rats. Whether alterations in developmental axonal remodeling mediate these effects awaits further studies.

Kainate receptor-mediated presynaptic inhibition at the mouse hippocampal mossy fibre synapse.

1. The presynaptic action of kainate (KA) receptor activation at the mossy fibre-CA3 synapse was examined using fluorescence measurement of presynaptic Ca2+ influx as well as electrophysiological recordings in mouse hippocampal slices. 2. Bath application of a low concentration (0.2 microM) of KA reversibly increased the amplitude of presynaptic volley evoked by stimulation of mossy fibres to 146 +/- 6 % of control (n = 6), whereas it reduced the field excitatory postsynaptic potential (EPSPs) to 30 +/- 4 %. 3. The potentiating effect of KA on the presynaptic volleys was also observed in Ca2+-free solution, and was partly antagonized by (2S, 4R)-4-methylglutamic acid (SYM 2081, 1 microM), which selectively desensitizes KA receptors. 4. The antidromic population spike of dentate granule cells evoked by stimulation of mossy fibres was increased by application of 0.2 microM KA to 160 +/- 10 % of control (n = 6). Whole-cell current-clamp recordings revealed that the stimulus threshold for generating antidromic spikes recorded from a single granule cell was lowered by KA application. 5. Application of KA (0.2 microM) suppressed presynaptic Ca2+ influx to 78 +/- 4 % of control (n = 6), whereas the amplitude of the presynaptic volley was increased. 6. KA at 0.2 microM reversibly suppressed excitatory postsynaptic currents (EPSCs) evoked by mossy fibre simulation to 38 +/- 9 % of control (n = 5). 7. These results suggest that KA receptor activation enhances the excitability of mossy fibres, probably via axonal depolarization, and reduces action potential-induced Ca2+ influx, thereby inhibiting mossy fibre EPSCs presynaptically. This novel presynaptic inhibitory action of KA at the mossy fibre-CA3 synapse may regulate the excitability of highly interconnected CA3 networks.

A hippocampal interneuron associated with the mossy fiber system

Network properties of the hippocampus emerge from the interaction of principal cells and a heterogeneous population of interneurons expressing gamma-aminobutyric acid (GABA). To understand these interactions, the synaptic connections of different types of interneurons need to be elucidated. Here we describe a type of inhibitory interneuron of the hippocampal CA3 region that has an axon coaligned with the mossy fibers. Whole-cell patch-clamp recordings, in combination with intracellular biocytin filling, were made from nonpyramidal cells of the stratum lucidum under visual control. Mossy fiber-associated (MFA) interneurons generated brief action potentials followed by a prominent after-hyperpolarization. Subsequent visualization revealed an extensive axonal arbor which was preferentially located in the stratum lucidum of CA3 and often invaded the hilus. The dendrites of MFA interneurons were mainly located in the strata radiatum and oriens, suggesting that these cells are primarily activated by associational and commissural fibers. Electron microscopic analysis showed that axon terminals of MFA interneurons established symmetric synaptic contacts predominantly on proximal apical dendritic shafts, and to a lesser degree, on somata of pyramidal cells. Synaptic contacts were also found on GABAergic interneurons of the CA3 region and putative mossy cells of the hilus. Inhibitory postsynaptic currents (IPSCs) elicited by MFA interneurons in simultaneously recorded pyramidal cells had fast kinetics (half duration, 3.6 ms) and were blocked by the GABA(A) receptor antagonist bicuculline. Thus, MFA interneurons are GABAergic cells in a position to selectively suppress the mossy fiber input, an important requirement for the recall of memory traces from the CA3 network.

Synaptic GABAA Activation Inhibits AMPA-Kainate Receptor–Mediated Bursting in the Newborn (P0–P2) Rat Hippocampus

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of "silent" glutamatergic synapses to conductive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses starts gradually after P2. Further, GABA via its depolarizing action seems to give rise to grossly synchronous yet slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study field potential recordings and gramicidin perforated and whole cell clamp techniques as well as K(+)-selective microelectrodes were used to examine the relative contributions of AMPA and GABA(A) receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. As early as postnatal day (P0-P2), highly coherent spontaneous firing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 +/- 3 s) consisting of 2.9 +/- 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R-mediated postsynaptic currents (PSCs) in simultaneously recorded pyramidal neurons (7.6 +/- 3.0 unitary currents per burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GABA(A)-R-mediated transmission appeared to exert inhibition in the CA3 pyramidal cell population. The GABA(A)-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABA(A)-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABA(A)-R currents was increased after muscimol application from 0.66 +/- 0.16 s(-1) to 1.43 +/- 0.29 s(-1). It was concluded that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0-P2 in rat hippocampus. Concurrently, although GABA(A)-R-mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.

Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses.

In hippocampal slices, synchronous CA3 network activity induced persistent strengthening of active positive-feedback synapses. This altered network operation by increasing probability of future synchronous network activation. Long-term depression of synaptic strength induced by partial blockade of NMDA receptors during synchronous network activity reversed changes in probability of spontaneous network activation. These results suggest that specific network activity patterns selectively alter strength of active synapses. Stable, reversible alterations in network activity can also be effected by corresponding alterations in synaptic strength. These findings confirm the Hebb memory model at the neural-network level and suggest new therapies for pathological patterns of network activity in epilepsy.

Model- and scale-independent performance of a hippocampal CA3 network architecture

The hippocampus is known to be a critical structure for memory function, but how its anatomical, physiological, and cellular elements endow it with this function remains a mystery. As such, even less is known about how neuropathological changes associated with Alzheimer's disease, epilepsy or traumatic brain injury lead to the clinical manifestations of disease. To begin to address these issues, we have constructed a biophysically detailed model of the CA3 region of the hippocampus that incorporates many of the well-characterized but, from a functional standpoint, poorly understood properties and phenomena into a functioning network. These include cholinergic neuromodulatory regulation, theta (4–6 Hz) oscillations, gamma (20–80 Hz) oscillations, diversity of interneuron classes, regular spiking vs. bursting pyramidal cells, and lamina-specific inputs and characteristic anatomy. We have found that the integration of these hippocampal elements results in a biological analog to the “connectionist” autoassociative attractor network where memories are represented as spatial patterns of temporally precise spikes across CA3. In addition, simulating the cholinergic modulation of this network model and its constituent cellular components suggests novel mechanisms for memory dysfunction in Alzheimer's disease E.D. Menschik, L.H. Finkel, Artificial Intell. Med. 13 (1994) 99–121; E.D. Menschik, L.H. Finkel, Progress in Brain Research, Elsevier, New York, in press. Here we demonstrate such networks to be robust and accurate in memory function, insensitive to the choice of neuronal model from a 64-compartment cell with numerous ionic conductances R.D. Traub et al., J. Physiol. 481 (1994) 79–95; to a reduced dual-compartment model P.F. Pinsky, J. Rinzel, J. Compu. Neurosci. 1 (1994) 39–60; and scalable from small to large networks.

Long-term depression of perforant path excitatory postsynaptic potentials following synchronous network bursting in area CA3 of immature hippocampus

Various forms of synaptic long-term potentiation and depression have been studied in detail in hippocampus and neocortex. [1, 2, 4, 9]Each are produced by specific patterns of synaptic activation and rely on electrical stimulation of afferents for their induction. Few studies have explored the ability of activity produced by cortical networks themselves to generate similar long-term changes in synaptic efficacy. Experiments have shown that periods of synchronized network bursting in both slices and dissociated cultures of hippocampus can lead to persistent network discharges. [16–18]Conversely, one study has reported that network discharging can disrupt the induction of long-term potentiation in hippocampus. [10]Whether long-term depression can be induced by synchronous network discharging is unknown. In experiments reported here, we examined the long-term effects of synchronized activity within hippocampal CA3 networks on synaptic potentials produced by the converging perforant path. Prior to induction of network bursting, slices were incubated in a perfusate containing picrotoxin and elevated (4 mM) Ca 2+ and Mg 2+. To induce network discharges, the concentration of both divalent cations were reduced to normal levels (1.5 mM). Following 20 min of network bursting, perforant path synapses, that did not participate in network discharging, underwent a 30% non-decrementing long-term depression. At the same time, synchronized network discharges, that were absent prior to induction, persisted upon return to preinduction conditions. The antagonist of the N-methyl- d-aspartate receptor, D(−)2-amino-5-phosphonovalerate, blocked both long-term depression of perforant path excitatory postsynaptic potentials and persistent network discharging. Results suggest that activity generated by hippocampal networks is able to produce long-term depression of non-coincidentally active synapses.

海馬ＣＡ１野のカオス時系列刺激依存性長期増強（ＬＴＰ）

In our previous report (Tsukada et al. (1996): Neural Networks, Vol. 9, pp. 1357-1365), the temporal pattern sensitivity of long-term potentiation (LTP) in hippocampal CA1 neurons was estimated by using Markov chain stimuli with different values of the serial correlation coefficient ρ1 between successive interstimulus-intervals. In this paper, the effect of chaotic stimuli on induction of LTP in the hippocampal CA1 area was investigated in comparison with those of Markov chain stimuli and periodic stimuli. The chaotic stimuli were produced by a modified Bernoulli map, so that interstimulus sequences with various values of ρ1 can be generated by changing the parameter B. These stimuli had an identical first order statistics (mean interstimulus-interval and variance), but their higher order statistics were different in the serial correlation coefficient as well as in fluctuation regarding the dynamic property of stimulus sequences. The LTP induced by chaotic stimuli with B=2 were significantly larger in magnitude than those of periodic stimuli and Markov chain stimuli, and also depended on the initial value of chaotic stimulus at B=2 and 3. These results suggest that chaotic signals play an important role for memory coding in the hippocampal CA1 network, and are discussed in relation to findings from a model simulation.

Presynaptic modulation of CA3 network activity.

The simultaneous discharge of hippocampal CA3 pyramidal cells is a widely studied in vitro model of physiological and pathological network synchronization. This network is rapidly activated because of extensive positive feedback mediated by recurrent axon collaterals. Here we show that population-burst duration is limited by depletion of the releasable glutamate pool at these recurrent synapses. Postsynaptic inhibitory conductances further limit burst duration but are not necessary for burst termination. The interval between bursts in vitro depends on the rate of replenishment of releasable glutamate vesicles and the probability of release of those vesicles at recurrent synapses. Therefore presynaptic factors controlling glutamate release at recurrent synapses regulate the probability and duration of synchronous discharges of the CA3 network.

Effects of GABA(A) inhibition on the expression of long-term potentiation in CA1 pyramidal cells are dependent on tetanization parameters.

Long-term potentiation (LTP) of excitatory synaptic responses of principal neurons in the hippocampus is accompanied by changes in GABAergic inhibition mediated by interneurons. The impact of inhibition on LTP of excitatory postsynaptic responses in CA1 pyramidal cells was assessed by monitoring changes in field potentials evoked by Schaffer collateral stimulation in hippocampal slices in vitro. First, to determine the effect of inhibition on population EPSPs, slices were exposed to the GABA(A) receptor antagonist bicuculline (10 microM). Both the slope and amplitude of field EPSPs (fEPSPs) were significantly enhanced by bicuculline indicating that inhibition modulates excitatory postsynaptic responses of pyramidal cells. To assess if stimulation-dependent changes in inhibition influence LTP of excitatory responses of pyramidal cells, LTP was examined in the presence and absence of bicuculline (20 microM) following either 100 Hz tetanization, or theta-patterned stimulation (short bursts delivered at 5 Hz). In normal medium, 100 Hz stimulation produced marked short-term potentiation that decayed 5-10 min post-tetanus and both stimulation paradigms produced similar LTP at 30 min post-tetanus. In comparison, LTP of the fEPSP slope and amplitude was significantly enhanced after theta-patterned stimulation, but not after 100 Hz stimulation, in bicuculline. The greater potentiation of field responses following theta-patterned stimulation in the presence of bicuculline indicates that a larger potentiation of excitatory responses was unmasked during suppression of inhibitory inputs. These results suggest that a long-lasting enhancement of inhibition in pyramidal cells was also induced following theta-patterned stimulation in normal ACSF. Since suppression of inhibition did not uncover a significantly larger potentiation following 100 Hz tetanization, the influence of inhibition on LTP of excitatory responses appears to be stimulation-dependent. In conclusion, theta-patterned stimulation appears to be more effective at inducing plasticity within inhibitory circuits, and this plasticity may partially offset concurrent increases in the excitability of the CA1 network.

Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.

Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function.

Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.

Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function.

Effect of adrenalectomy in kindled rats.

It has previously been observed that adrenalectomy (ADX) increases the amplitude of transient Ca currents in CA1 hippocampal neurons. In the present study, the effect of ADX on cellular properties of CA1 neurons was investigated under conditions that challenge the CA1 network, i.e. in fully kindled rats, 5-6 weeks after the last kindling session. At this time, adrenally intact kindled rats showed, in comparison to non-kindled controls, a reduced population spike amplitude evoked in the CA1 area by Schaffer/commissural fiber stimulation, an increased amplitude of low-threshold, transient Ca currents and a decrease of the high-threshold, sustained Ca currents. As observed before, ADX in non-kindled rats increased the amplitude of transient Ca currents while sustained Ca currents were not affected. In kindled rats, ADX did not increase the transient Ca current amplitude beyond the level reached by kindling alone. The kindling-induced reduction of the sustained Ca current was partly normalized after ADX. Field responses of kindled rats were not affected by ADX. These data support the view that lack of adrenal hormones does not exacerbate but, to some extent, normalizes the kindling-induced changes in cellular properties and network function of the CA1 area. The hormonal effects on kindling may be reciprocal in nature, since kindling, in turn, was found to affect the stress response and the corticosteroid receptor mRNA expression in the hippocampus.