CA1 Units Research Articles

Carbon and oxygen isotope microanalysis of calcite in the Permian Kupferschiefer system, Saale subbasin, eastern Germany

The Kupferschiefer district in Central Europe contains some of the world's highest-grade sediment-hosted stratiform Cu (SSC) deposits. In the Saale subbasin (eastern Germany), high-grade sulfides formed via replacement of calcite cement in the continental sandstones of the uppermost Rotliegend (S1), the overlying organic-rich marine mudstones of the Kupferschiefer (T1) and the Zechstein Limestone (Ca1) units. The spatial distribution of the calcite cement, therefore, had a fundamental role to play in the Cu mineralizing system. In this study, we investigate the origin of the calcite cement (and crosscutting calcite veins) using detailed petrography (cathodoluminescence, CL; scanning electron microscopy, SEM), major element chemistry (electron probe microanalyzer, EPMA), and secondary ion mass spectrometry (SIMS) microanalyses of δ13C and δ18O values in drill core samples (n = 47) from the Saale subbasin. The calcite cement in the S1, T1 and Ca1 has a similar CL response and major element chemistry, suggestive of a common origin. Overlapping δ13C and δ18O values in calcite cement in samples from the S1 and T1 in the Sangerhausen and Wallendorf drill cores also suggest that the calcite cement was derived from fluids of similar composition. The low δ13C values of calcite cement in samples from the S1 (−13‰ to 4.3‰, VPDB) and T1 (−10‰ to 0.7‰) indicates carbonate alkalinity was sourced mainly from seawater-derived fluids and the oxidation of organic matter. The wide range of δ18O values in the calcite cement in the S1 (∼18‰ to 31‰, VSMOW) and T1 (∼ 22‰ to 31‰) samples suggest they are derived from pore fluids with a chemical composition influenced by early diagenetic alteration of detrital clasts, mainly dissolution of volcanic rock fragments, with minor contributions from the influx of meteoric waters and evaporated seawater. The negative δ13C values (down to −15‰) in calcite veins from the T1 and Ca1 indicate sources of carbonate alkalinity derived from organic matter degradation. Our data demonstrate that no isotopic hydrothermal alteration haloes can be inferred from the δ13C and δ18O values in calcite cement associated with the high-grade sulfide mineralization. The lack of systematic isotopic variability in the calcite cement likely indicates the mineralizing fluid flux or temperature was not sufficient to overprint the background sources of isotopic variability, which may help to explain the modest size of SSC deposits in this part of the Kupferschiefer district.

Enhancement of Hippocampal-Thalamocortical Temporal Coordination during Slow-Frequency Long-Duration Anterior Thalamic Spindles.

Temporal nesting of cortical slow oscillations, thalamic spindles, and hippocampal ripples indicates multiregional neuronal interactions required for memory consolidation. However, how the thalamic activity during spindles organizes hippocampal dynamics remains largely undetermined. We analyzed simultaneous recordings of anterodorsal thalamus and CA1 in male mice to determine the contribution of thalamic spindles in cross-regional synchronization. Our results indicated that temporal hippocampo-thalamocortical coupling was more enhanced during slower and longer thalamic spindles. Additionally, spindles occurring closer to slow oscillation trough were more strongly coupled to ripples. We found that the temporal association between CA1 spiking/ripples and thalamic spindles was stronger following spatial exploration compared with baseline sleep. We further developed a hippocampal-thalamocortical model to explain the mechanism underlying the duration and frequency-dependent coupling of thalamic spindles to hippocampal activity. Our findings shed light on our understanding of the functional role of thalamic activity during spindles on multiregional information transfer.SIGNIFICANCE STATEMENT The contribution of thalamic spindles with differential properties to cross-regional synchronization and information transfer still remains poorly understood. Using simultaneous anterodorsal thalamic and hippocampal recordings from naturally sleeping mice before and after exploration, we found strong coupling of CA1 units to anterodorsal thalamic spindles and increase of this coupling following spatial experience. We further showed that the temporal coupling of CA1 units and hippocampal ripples with thalamic spindles and the spindle-associated modulation of CA1 units with ripples were stronger for spindles with slower frequency of oscillations. Our experimental as well as computational findings using a hippocampal-thalamocortical model provide the first demonstration that spindle frequency and duration can provide valuable information about the underlying multiregional interactions essential for memory consolidation computations.

Learning a New Path to Reward: Hippocampal Signals Modify Orbitofrontal Representations

To adapt to changing circumstances, we often recall similar situations and the consequences of past choices. Memory for recent events requires the hippocampus (HPC); using memory to adapt to a new circumstance can require the orbitofrontal cortex (OFC). Spatial learning is impaired by HPC but not by OFC dysfunction. Rather, learning an unfamiliar reversal of a well-established contingency is impaired by OFC dysfunction, suggesting that learning a new spatial path to reward requires both structures and their interactions. To investigate possible interactions, we simultaneously recorded OFC and HPC subregion CA1 ensembles as rats learned spatial reversals in a plus maze. CA1 and OFC units fired differentially across maze locations, and spiking recorded in the start arms in each structure predicted pending choices. Striking interactions between the structures occurred only while rats learned an unfamiliar reversal: (1) OFC spiking phase locked to hippocampal theta oscillations. (2) Mixed pairs of CA1 and OFC neurons fired together within single theta cycles. (3) CA1 population vectors (PVs) predicted changes in OFC activity, but not vice versa. (4) Spatial representations decoded from PVs in the two structures differed: CA1 ensembles stably represented distinct spatial journeys, whereas OFC ensembles developed more generalized goal arm representations in different paths to identical rewards. That these dynamics occurred only during learning an unfamiliar reversal, not during stable performance or familiar reversals, suggests that unique frontotemporal interaction mechanisms are engaged selectively when new task features come to guide decision-making.

MPFC spindle cycles organize sparse thalamic activation and recently active CA1 cells during non-REM sleep.

Sleep oscillations in the neocortex and hippocampus are critical for the integration of new memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood. To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; slow/delta; spindles), we recorded units and local field potentials (LFPs) simultaneously in the limbic thalamus, mPFC, and CA1 in rats. We report that the cycles of neocortical spindles provide a key temporal window that coordinates CA1 SWRs with sparse but consistent activation of thalamic units. Thalamic units were phase-locked to delta and spindles in mPFC, and fired at consistent lags with other thalamic units within spindles, while CA1 units that were active during spatial exploration were engaged in SWR-coupled spindles after behavior. The sparse thalamic firing could promote an incremental integration of recently acquired memory traces into neocortical schemas through the interleaved activation of thalamocortical cells.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4–9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus.

Schaffer-Specific Local Field Potentials Reflect Discrete Excitatory Events at Gamma Frequency That May Fire Postsynaptic Hippocampal CA1 Units

Information processing and exchange between brain nuclei are made through spike series sent by individual neurons in highly irregular temporal patterns. Synchronization in cell assemblies, proposed as a network language for internal neural representations, still has little experimental support. We use a novel technique to extract pathway-specific local field potentials (LFPs) in the hippocampus to explore the ongoing temporal structure of a single presynaptic input, the CA3 Schaffer pathway, and its contribution to the spontaneous output of CA1 units in anesthetized rat. We found that Schaffer-specific LFPs are composed of a regular succession of pulse-like excitatory packages initiated by spontaneous clustered firing of CA3 pyramidal cells to which individual units contribute variably. A fraction of these packages readily induce firing of CA1 pyramidal cells and interneurons, the so-called Schaffer-driven spikes, revealing the presynaptic origin in the output code of single CA1 units. The output of 70% of CA1 pyramidal neurons contains up to 10% of such spikes. Our results suggest a hierarchical internal operation of the CA3 region based on sequential oscillatory activation of pyramidal cell assemblies whose activity partly gets in the output code at the next station. We conclude that CA1 output may directly reflect the activity of specific ensembles of CA3 neurons. Thus, the fine temporal structure of pathway-specific LFPs, as an accurate readout of the activity of a presynaptic population, is useful in searching for hidden presynaptic code in irregular spikes series of individual neurons and assemblies.

Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long-term potentiation in vivo

Long-term potentiation (LTP) is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes it difficult to estimate the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs) in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency) that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average (STA) of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway-specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. They indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

Rhythms of sleep: orchestrating memory consolidation (Commentary on Clemens et al.)

During sleep, consolidation of declarative memory is thought to be mediated by a ‘dialogue’ between hippocampal and neocortical networks, promoting the reorganization of recent memory traces (Buzsaki, 1996; Clemens et al., 2005). Consistent with this hypothesis, several rodent studies have established a temporal relationship between 12 and 15 Hz cortical sleep spindle oscillations and high-frequency ripple bursts originating in the hippocampus (Clemens et al., 2006, 2007, 2011). Both spindles and ripples are thought to facilitate synaptic plasticity and the consolidation of memory. An accumulating body of evidence indicates that network-level ‘reactivation’ of recent experience occurs during ripple bursts in rodents (Ji & Wilson, 2007; Marshall & Born, 2007), while human studies demonstrate that spindle activity during post-learning sleep predicts enhanced retention of recently learned material (Siapas & Wilson, 1998; Sirota et al., 2003; Schabus et al., 2004; O’Neill et al., 2010). Nevertheless, the dynamics underlying a potential role for spindle–ripple interactions in cortical plasticity remain largely unknown. In their new study, Clemens et al. (2011); (this issue) report the first human data examining millisecond-timescale temporal interactions between hippocampal ripples and cortical sleep spindles. Intracranial EEG data were acquired in epilepsy patients from implanted parahippocampal foramen ovale electrodes, which the authors have previously established as sensitive for detecting 80–140 Hz ripple bursts similar to those described in the hippocampus proper (Sirota & Buzsaki, 2005). Clemens et al. (2011) demonstrate a correlation between spindles and hippocampal ripples on two distinct timescales. First, in line with the findings of prior studies (Sirota & Buzsaki, 2005; Clemens et al., 2006, 2007, 2011), ripple activity was increased during the ± 1 s window surrounding spindles. More significantly, however, Clemens and colleagues also found that ripple bursts were tightly phase-locked to the ‘troughs’ of the individual oscillations comprising a spindle (at which time neuronal excitation presumably reaches a maximum), with ripple activity reaching a peak just a few milliseconds prior to each trough. This phase-locking of ripples to spindle troughs on a millisecond timescale has been reported in only one prior study [in rodents (Clemens et al., 2007)], and is relevant to elucidating mechanisms of sleep-dependent plasticity for several reasons. Firstly, coordinated activity on this timescale cannot be explained via a generic influence of the < 1 Hz cortical slow oscillation, known to group sleep rhythms on the multi-second timescale (Steriade, 2003; Tamminen et al., 2010), suggesting there may be a particular functional significance for these more precisely timed interactions between ripples and spindles. Secondly, this observation supports the longstanding suggestion that hippocampal output during ripple bursts induces plasticity in cortical targets: as ripples are associated with the ‘reactivation’ of specific recent memory traces, timing their expression to maximally excitatory phases of a spindle could optimally facilitate hippocampus-mediated cortical plasticity. Interestingly, Clemens et al. (2011) found that ripple activity consistently peaks just prior to spindle troughs. In contrast, Sirota et al. (2003) reported that both ripples and CA1 unit activity peaked approximately 50 ms after spindle troughs in rodents, speculating that neocortical activity exerted a modulating influence on hippocampal networks, triggering the expression of ripples. The present findings may prompt some renewed discussion about the causal direction of this particular hippocampal–cortical interaction, as some models of sleep-dependent memory consolidation favor the notion that hippocampal memory reactivation during ripple bursts should exert a driving influence on mechanisms of plasticity in the cortex rather than vice versa. Regardless of such remaining questions, these observations by Clemens and colleagues add an important level of nuance to our understanding of oscillatory brain dynamics underlying sleep-dependent memory consolidation in humans, providing further evidence that the functional significance of sleep spindles lies in their facilitation of hippocampus-mediated cortical plasticity during sleep.

Self-Motion and the Hippocampal Spatial Metric

Self-motion signals are sufficient for animal navigation ("path integration") and for updating hippocampal location-specific firing. The contributions of ambulatory, vestibular, and optic self-motion signals to CA1 unit activity and EEG were studied while rats either walked or drove a car between locations on a circular track (referred to as WALK and CAR, respectively) or experienced pseudomotion, in which the animal was stationary and the environment was rotated (WORLD). Fewer pyramidal cells expressed place fields during CAR and those that did exhibited substantially larger place fields. The number of theta cycles required to traverse a place field increased, whereas the slope of the theta phase of firing versus position function was reduced. The presence and/or location of place fields were not well correlated between conditions. These effects were even more accentuated during WORLD. These results are not explainable by a simple "smearing out" of place fields but, in terms of size of place fields relative to the track size, are comparable with what would be observed if the track circumference was reduced and the animal moved around it at a correspondingly slower speed. Theta (and its 14-18 Hz harmonic) power were dependent on velocity, but the gain of this function was substantially reduced during CAR and WORLD, again as if the rat were moving more slowly. The spatial scale over which the hippocampal population vector is updated appears to be derived primarily from the gain of a self-motion velocity signal with approximately equal components derived from ambulation, vestibular, and optic-flow signals.

Single Neurons in the Dentate Gyrus and CA1 of the Hippocampus Exhibit Inverse Patterns of Encoding During Trace Fear Conditioning.

Trace fear conditioning is a hippocampus-dependent learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single-neuron activity was recorded simultaneously from the dentate gyrus (DG) and CA1 of rats during unpaired pseudoconditioning and subsequent trace fear conditioning. Single neurons in DG showed a progressive increase in learning-related activity to the CS and US across trace fear conditioning. Single neurons in CA1 showed an early increase in responding to the CS, which developed into a decrease in firing later in trace conditioning. Correlation analyses showed that DG and CA1 units exhibit inverse patterns of responding to the CS during trace fear conditioning.

Analysis of recordings of single-unit firing and population activity in the dorsal subiculum of unrestrained, freely moving rats.

We examined neuronal activity in the dorsal subiculum of unrestrained, male adult Wistar rats, which were implanted with a moveable eight-electrode microdrive. The subiculum is the primary hippocampal formation output area and is comparatively uninvestigated neurophysiologically. We compared subicular unit activity and the subicular EEG while rats occupied a small, restricted environment and also correlated neuronal activity with the ongoing behavior of the animal. Units were separated using their electrophysiological characteristics into bursting units, regular spiking units, theta-modulated units, and fast spiking units. The bursting and regular spiking unit classes are similar to hippocampal CA1 units, whereas the fast spiking units appear to be interneurons. Bursting units were variable in their behavior: some units bursted regularly, and others bursted only occasionally. Theta-modulated units have not been described before; these were similar to regular spiking units in all respects except that they increased their firing significantly when theta oscillations were present in the simultaneous EEG record. Subicular EEG was similar to hippocampal EEG, with theta oscillations dominating "alert, moving" behaviors, while large amplitude irregular activity (LIA), which included sharp waves, predominated when theta oscillations were not present, mainly during "alert, still" and "quiet" behaviors. A relatively small proportion of subicular recordings (approximately 32%) were phase-locked to theta; this is a smaller proportion than in areas from which the subiculum takes major inputs. The relative lack of entrainment of subicular neurons by this important intrinsic rhythm is suggestive of a limit to which theta might be capable of affecting both subicular and hippocampal information processing more generally.

Induction and transient suppression of long-term potentiation in the peri- and postrhinal cortices following theta-related stimulation of hippocampal field CA1

During behavioral events associated with periods of likely mnemonic processing, CA1 pyramidal cells in rats typically discharge repetitively in either high-frequency bursts (`complex spikes') or single spikes, both of which are tightly phase-locked to the hippocampal theta rhythm. Interestingly, patterned stimulation which mimics the repetitive, learning-related complex spike discharges are optimal for inducing long-term potentiation (LTP) of excitatory field potentials in CA1, and patterned stimulation which mimics the theta-related single action potentials results in a robust and lasting depotentiation at these same synapses. The aim of the present study was to determine the extent to which these physiologically-relevant patterns of hippocampal stimulation have similar effects on synaptic efficacy in the monosynaptic projection from CA1 to the perirhinal and postrhinal cortices (PRh), areas thought to play a prominent role in many forms of learning and memory. Single-pulse stimulation of CA1 evoked a small amplitude, short latency population excitatory postsynaptic potential (EPSP) in the PRh. Theta-burst stimulation (TBS; n=8) delivered to CA1 reliably potentiated the PRh EPSP slope for at least 30 min. Theta-pulse stimulation (TPS; 5 Hz; n=4) delivered to CA1 5 min after TBS substantially but transiently suppressed EPSP slope relative to that of potentiated control preparations. Collectively these data suggest that theta-related patterns of hippocampal activation can reliably induce and transiently suppress LTP in PRh, and are consistent with the notion that behaviorally-relevant, theta-modulated patterns of CA1 unit activity may result in both long- and short-term alterations of synaptic strength within their rhinal cortical targets.

Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat

The septal and temporal poles of the hippocampus differ markedly in their anatomical and neurochemical organization. Although it is well established that the internal representation of space is a fundamental function of hippocampal neurons, most of what is known about spatial coding in the hippocampus of freely moving animals has come from recordings from the dorsal one-third (largely for technical convenience). The present study therefore compared the spatial selectivity of CA1 neurons in the dorsal and ventral hippocampi of rats during performance of a food reinforced, random search task in a square chamber containing simple visual landmarks. Neural activity was recorded in the dorsal and ventral hippocampi of opposite hemispheres in the same rats, in many cases simultaneously. As in dorsal hippocampus, ventral CA1 units could be classified as "complex spike" (pyramidal) cells or "theta" interneurons. Both dorsal and ventral theta cells fired at relatively high rates and with low spatial selectivity in the apparatus. Of the population of complex spike cells in the ventral hippocampus, a significantly smaller number had "place fields" than in the dorsal hippocampus, and the average spatial selectivity was of significantly lower resolution than that found among dorsal hippocampal complex spike cells. Thus, a septotemporal difference of spatial selectivity was found in the CA1 field of the rat hippocampus, complementing many other anatomical and neuropharmacological studies. A number of possible functional interpretations can be suggested from these results, including a computational advantage of representing space at different scales or a preeminence of essentially nonspatial information processing in the ventral hippocampus.

Involvement of auditory cortical and hippocampal neurons in auditory working memory and reference memory in the rat

The goal of the present study was to see whether one neuron is involved exclusively in one type of memory or in different types of memory. Single-unit activity was recorded from rat hippocampal CA1, CA3, dentate gyrus, and auditory cortex (AC) during performances of auditory working memory (WM) and reference memory (RM) tasks. Both the memory tasks employed identical apparatus and stimuli and differed only in the type of memory required for correct performance. Around 10% and 43% of the units from the four brain regions showed sensory correlates (differences in activity due to the type of sensory stimulus) only in the WM or RM task, respectively. Only the AC had units showing different kinds of sensory correlates between the WM and RM tasks. About 30% of the units from the four regions had sensory-retention correlates (sustained differential activity during the delay) only in the RM task, whereas the AC had units with sensory-retention correlates only in the WM task or in both the WM and RM tasks. Approximately 35% of the units from the hippocampal regions showed motor correlates (increments of activity immediately prior to responses) only in the WM task. Another 30% of the hippocampal units showed such correlates both in the WM and RM tasks. About 22% of the hippocampal CA1 and CA3 units showed comparison-motor correlates (increases of activity prior to correct responses) only in the WM task. These results indicate that some neurons are involved solely in WM or RM, whereas other neurons are involved in both WM and RM. The results also suggest that more neurons are involved in sensory and retention processing for RM than for WM, and that the AC alone has flexible neurons involved in the processes for both types of memory. More hippocampal neurons are involved in the motor and comparison processes for WM than for RM.

Hippocampal plasticity during jaw movement conditioning in the rabbit

Hippocampal CA1 unit responses were recorded during classical conditioning of rhytmic jaw movements in New Zealand White rabbits. Training was accomplished using a 1 kHz tone as the conditioned stimulus (CS) and 1 ml of sweetened water as the unconditioned stimulus (US). The interstimulus interval was 250 ms. Daily sessions consisted of 48 paired trials and six tonealone test trials, with an intertial interval averaging 60 s. Controls were given explicity unpaired stimuli. Unit and behavioral conditioned responses developed very rapidly in the trained group, but did not occur in controls. Averaged unit poststimulus histograms showed a correspondence between rhytmic cell discharges and the periodicity of the behavioral conditioned response after training. The results are discussed in relation to a hippocampal role in the modulation of learned movement patterns.

Distribution of GABA sensitive areas on hippocampal pyramidal cells.

In isolated transverse hippocampal slices GABA (gamma-amino-butyric acid) was applied iontophoretically to various parts of the dendritic tree of CA1 pyramidal cells. Indices of GABA effects were reduced amplitude of orthodromically driven CA1 population spikes and inhibition of single CA1 units driven by orthodromic stimulation or by application of L-glutamate. Weak iontophoretic currents of GABA (3-6 nA, backing current -3 nA) effectively reduced the amplitude of the population spike and arrested unit activity when applied in a position close to the soma. The effect was halved when GABA was applied 25-30 micrometer away at right angles to the main dendritic axis. In the direction of the main dendritic axis, GABA was affective as far as 250 and 150 micrometer from the soma in the apical and basal dendritic directions, respectively, corresponding to about 50% of the total dendritic length. The best effect was usually found at a depth corresponding to that of the recording electrode, probably because the main dendritic axis was parallel to the slice surface. The sharp localization of GABA sensitivity when applied in the pyramidal layer supports earlier evidence that GABA mediates the basket cell inhibition on the soma of the pyramidal hippocampal cells. In the dendritic tree, GABA may also have an inhibitory function with an effectiveness matching that of the soma application.