Theta Cells Research Articles

Theta‐ and movement velocity‐related firing of hippocampal neurons is disrupted by lesions centered on the perirhinal cortex

The hippocampus is critically involved in spatial memory and navigation. It has previously been proposed that, as part of this process, the hippocampus might have access to self-motion information. The possibility that some of this information may originate from the perirhinal cortex, a region involved in high-order multimodal processing, was tested in the present study by recording the responses of hippocampal complex-spike (place cells) and theta cells (putative interneurons) to movement velocity and to the movement-related theta rhythm EEG while rats with bilateral ibotenic acid lesions centered on the perirhinal cortex (n = 5), or control surgeries (n = 5), foraged in a rectangular environment. Perirhinal cortex lesions altered several characteristics of place and theta cell firing. First, the proportion of theta cells recorded was significantly lower in perirhinal lesion animals (8/39 units) compared to controls (22/53 units). Second, the firing of place cells recorded from lesion animals was phase-shifted so as to occur significantly earlier during the theta rhythm cycle than in place cells from controls (mean difference = 48.73 degrees). Third, the firing rates of a significantly lower proportion of place cells from lesion animals were modulated by the movement velocity of the animal compared to place cells from controls. These results indicate that the perirhinal cortex contributes to the responses of hippocampal CA1 place cells by providing information about self-movement and by controlling the timing of firing of these cells. This information may normally be utilized by the hippocampus during spatial memory and navigation processes.

Recognition Memory Correlates of Hippocampal Theta Cells

Investigations of hippocampal theta cell activity have typically involved behavioral tasks with modest cognitive demands. Recordings in rats locomoting through space or engaged in simple stimulus discrimination or conditioning have revealed some place specificity and S(+)/S(-) selectivity in addition to the hippocampal EEG theta-related behavioral/motor correlates. However, little data exist regarding theta cell activity during performance of more cognitively demanding, hippocampal-dependent recognition memory tasks. Here, we examined the cognitive firing correlates of theta cells in rats that were performing an olfactory recognition memory task with distinct sample and test phases. Discriminant analysis revealed odor and match/nonmatch memory correlates in theta cell activity comparable in relative magnitude to that of the principal cells. Odor-specific theta cell responses in the sample phase were restricted primarily to CA1 and linked to task performance. In the test recognition phase, match/nonmatch theta cells were found primarily in the CA3 and CA1 fields, most of which exhibited greater activity on correct nonmatch trials in which recognition occurred than on error match trials in which recognition failed. Odor selectivity of the match/nonmatch signaling was greatest in the dentate gyrus (DG) and CA3 and least in CA1. This inverted pattern of stimulus specificity in the sample versus test phase was similar to that observed in principal cells but with a greater contrast between the CA1 and DG/CA3 fields. Together, these findings suggest that theta cells actively participate in hippocampal recognition memory processing and play a specific role in shaping the cognitive firing properties of the hippocampal principal cells.

Sequence of single neuron changes in CA1 hippocampus of rabbits during acquisition of trace eyeblink conditioned responses.

The sequence of changes in single neuron activity in the CA1 area of the rabbit hippocampus was examined during daily sessions (80 trials/session) of hippocampally dependent nonspatial trace eyeblink (i.e., nictitating membrane response) conditioning. Each trial for trace conditioned animals (n = 7) consisted of a tone conditioned stimulus (CS; 6 kHz; 90 dB, 100 ms) followed by a 500-ms silent trace period, then a corneal airpuff unconditioned stimulus (US; 3.0 psi; 150 ms). Control animals (n = 5) received unpaired CSs and USs. Most pyramidal (n = 309) and theta (n = 21) cells were recorded for a single day of training. The activity of cells for each animal were grouped according to: the day of training that CRs began to increase and the day of training that CR performance became asymptotic. Pyramidal cells from trace conditioned animals demonstrated several stages of learning-related activity: large increases in activity after both the CS and US early in conditioning on the day of training when CRs began to increase, smaller moderate increases in activity on the following days of training, and decreases in activity after the US during asymptotic CRs. Pyramidal cell-increases declined significantly across the trials of each daily session. Theta cells showed an activity pattern opposite to the pyramidal cells, consistent with the notion that theta cells have an inhibitory influence on pyramidal cells. Single pyramidal cells also were categorized into response profiles. Most pyramidal response profiles showed increases in activity specific to the day of initial CRs. Two of the pyramidal response profiles may be involved in assessing the temporal properties of the CS-US trace conditioning trial.

Midbrain raphe cell firing and hippocampal theta rhythm in urethane-anaesthetized rats.

This study aimed to examine the functional coupling between midbrain raphe and the septohippocampal system at the level of neuronal firing. Raphe unit activity and hippocampal EEG were simultaneously recorded in urethane-anaesthetized rats and their relationship was examined in the frequency domain. Subsets of presumably non-serotonergic neurones in both the dorsal and median raphe nuclei fired rhythmically in synchrony with hippocampal theta activity. Theta cells in the median raphe showed higher coherence than those in dorsal raphe and formed a more homogeneous group of cells, according to their firing rates. Since the raphe-septal serotonergic system is known to desynchronize the hippocampal EEG, activation of a subset of nonserotonergic cells during theta in this nucleus indicates a feedback from the limbic circuitry on the ascending raphe control of forebrain activity.

Place cells recorded in the parasubiculum of freely moving rats.

Previous studies have identified neurons in the hippocampus, subiculum, and entorhinal cortex which discharge as a function of the animal's location in the environment. In contrast, neurons in the postsubiculum and anterior thalamic nucleus discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Because the parasubiculum (PaS) has extensive connections, either directly or indirectly, with these structures, it is centrally located to influence the neuronal activity in these areas. This study was therefore designed to determine the types of behavioral and spatial correlates in neurons from the PaS. Single unit recordings were conducted in the PaS of freely moving rats trained to retrieve food pellets thrown randomly into a cylindrical apparatus. A total of 10.3% of the cells were classified as place cells because they discharged in relation to the animal's location in the cylinder. A large percentage of cells (41.4%) were classified as theta cells. The remaining cells had nondiscernable behavioral correlates. Quantitative analysis of the firing rate maps for the place cells showed they had higher levels of background activity and contained larger firing fields than values reported previously for hippocampal place cells. Directional analysis showed that only three out of 16 cells contained a secondary directional correlate; the firing rate for the remaining cells was not affected by the animal's directional heading within the firing field. A time shift analysis, which shifted the spike time series relative to the animal location series, was conducted to determine whether the quality of the location-specific firing could be improved. The time shifts for three different spatial parameters were optimal when cell discharge led the animal's position. Furthermore, the optimal time shifts for two of these parameters (firing area and information content) were less than the optimal shift reported for hippocampal place cells and suggested that PaS cell discharge lagged behind hippocampal place cell activity. Rotation of the cue card with the animal out of view led to near equal rotation of the firing field when the animal was returned to the apparatus. These results indicate that a small population of cells in the PaS encode the animal's location in its environment, although the representation of space encoded by these cells is different from the type of representation encoded by hippocampal place cells.

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.

Simultaneous single-cell recording and microdialysis within the same brain site in freely behaving rats: a novel neurobiological method

We present a method for performing intracerebral microdialysis in freely behaving rats while recording the firing of neurons within the dialysis site. Studying hippocampal theta cells and complex-spike cells with this technique, it has been found that: (1) when the microdialysis fluid contained only artificial cerebrospinal fluid, both types of neurons displayed normal electrical activity, (2) the simultaneous single-cell recording/microdialysis procedure could be readily performed for as long as 3 days, and (3) inclusion of drugs into the microdialysis fluid, at appropriate concentrations, caused clear changes in firing pattern. For example, microdialysis with 1% lidocaine completely abolished, whereas that with 50 mM K + markedly increased, the neuronal electrical activity. These cellular changes developed without apparent EEG or behavioral manifestations and were reversible. In some of the experiments, the extracellular concentrations of glutamate and aspartate in the recording/dialysis site were also measured. The described method allows the extracellular environment of recorded brain cells to be manipulated by drugs delivered through the microdialysis probe and simultaneously allows determination of the neurochemical composition of that environment over a remarkably long period of time and in intact, physiologically functioning, neural networks. Such studies will provide new insights into the molecular basis of neuronal activity in the brain in the context of behavior, including learning.

Spatial information content and reliability of hippocampal CA1 neurons: effects of visual input.

The effects of darkness on quantitative spatial firing characteristics of 235 hippocampal CA1 "complex spike" (CS) cells were studied in young and old Fischer-344 rats during food-motivated performance of a randomized, forced-choice task on an eight-arm radial maze. The room lights were turned on or off on alternate blocks of all eight arms. In the dark, a lower proportion of CS cells had "place fields," and the fields were less specific and less reliable than in the light. A small number of cells had place fields unique to the dark condition. Like CS cells, Theta cells showed a reduction in spatially related firing in the dark. The specificity and reliability of the place fields under both light and dark conditions were similar for both age groups. Increasing the salience of the environment, by increasing the light level and the number of visual cues in the light condition, did not affect the specificity or reliability of the place fields. Even though all rats had substantial prior experience with the environment, and were placed on the maze center under normal illumination before the first dark trial, the correlation between the firing pattern in the light and dark increased after the rat first traversed the maze in the light. Thus, even after considerable experience with the environment over days, experiencing the illuminated environment from different locations on a given day was a significant factor affecting subsequent location and reliability of place fields in darkness. While the task was simple and errors rare, rats that made fewer errors (i.e., re-entries into the previously visited arm) also had more reliable place cells, but no such correlation was found with place cell specificity. Thus, the reliability of spatial firing in the hippocampus may be more important for spatial navigation than the size of the place fields per se. Alternatively, both spatial memory and place field reliability may be modulated by a common variable, such as attention.

Disinhibition of hippocampal pyramidal cells during the transition into theta rhythm.

The activity of hippocampal complex-spike cells (presumed pyramidal cells) and theta cells (presumed interneurons) was examined during transitions from non-theta electroencephalogram (EEG) states to theta EEG states in freely moving and sleeping rats. Theta cell firing rates were significantly depressed in a 1-s period centered on the EEG transition relative to the surrounding 1-s periods (normalized rates +/- SEM): 1.05 +/- 0.02 for the "non-theta" period, 0.59 +/- 0.03 for the "transition" period, and 1.36 +/- 0.04 for the "theta" period (n = 26 cells). Conversely, complex-spike cell firing was significantly increased during the transition period: 0.51 +/- 0.11 for the "non-theta" period, 2.24 +/- 0.19 for the "transition" period, and 0.24 +/- 0.04 for the "theta" period (n = 27 cells). This diametrically altered activity indicates that theta cells must be actively inhibited during the transition. The increased activity in complex-spike cells during the transition may be simply a release from inhibitory control by interneurons. The pattern of theta cell inhibition together with increased complex-spike cell activity appears to be a general property of transitions into the theta EEG state, irrespective of behavior. It is suggested that increased activity in septal afferents (GA-BAergic cell activity greater than cholinergic cell activity) initially inhibits hippocampal interneurons. The inhibition is not sustained because of an activity-dependent decrease in the potency of the septointerneuronal inhibition, leaving the rhythmic excitatory (cholinergic) septointerneuronal inputs, together with principal cell inputs, to increase interneuron firing rates.

Differential effects of age on subpopulations of hippocampal theta cells

The possible contribution of age-related changes in the firing properties of hippocampal theta cells to spatial learning deficits was addressed in the present study. The behavioral correlates of theta cells in strata oriens, pyramidale, and granulosum were compared as young and old rats performed a radial maze spatial working memory task. Behaviorally, the old animals made significantly more errors on the maze and required more time to solve the task than did young animals. Firing rates were compared in four different locomotion states: still, running radially inward and radially outward, and forwadd motion. The discharge rates of theta cells in strata pyramidale and granulosum were significantly modulated by these movements in both age groups. Stratum oriens theta cells recorded from young animals, on the other hand, were not movement-sensitive, while similar cells from old animals demonstrated exaggerated responses to movement. In old animals, the mean discharge rates were higher in stratum granulosum and lower in stratum oriens than in the young rats. The discharge rates of cells in stratum pyramidale did not differ between age groups. These region specific changes in the firing characteristics of hippocampal theta cells are likely to have important consequences for information processing in this structure.

Effects of atropine on hippocampal theta cells and complex-spike cells

The medial septal nuclei are essential for the naturally occuring hippocampal theta rhythm. Evidence that the rhythmic activity of the septum is carried via cholinergic afferents to the hippocampus has been: (a) the existence of a cholinergic septo-hippocampal projection, and (b) the sensitivity of one type of theta rhythm to antimuscaranic agents or cholinergic depletion. The muscarinic action of acetylcholine on pyramidal cells, however, is too slow to carry even a 4 Hz signal. Recent in vitro studies have confirmed a fast excitatory response by some hippocampal interneurons to muscarinic agonists. In urethane anesthetized rats, iontophoretic application of atropine to 17 hippocampal theta cells (presumed interneurons) during the theta rhythm, reduced their firing rates to an average of 24% of control rates. The effect of iontophoretic atropine application to 4 CA1 complex-spike cells (presumed pyramidal cells) was a selective elimination of their bursting activity with no significant effect on overall firing rate. The data suggest that: (1) interneuronal firing, during the hippocampal theta rhythm, is dominated by an excitatory cholinergic input and not by exctatory collaterals of pyramidal cells; (2) somatic burst firing by CA1 pyramidal cells requires the presence of acetylcholine.

Nimodipine enhances spontaneous activity of hippocampal pyramidal neurons in aging rabbits at a dose that facilitates associative learning

The functional activity of hippocampal neurons is strongly correlated with behavioral performance in a vertebrate model learning system, rabbit eyeblink conditioning. Using this system, we have previously shown that (a) complete removal of the hippocampus blocks acquisition of the conditioned response; (b) a calcium-dependent postsynaptic afterhyperpolarization is reduced in pyramidal cells recorded intracellularly in hippocampal slices taken from conditioned rabbits; and (c) nimodipine, a 1,4-dihydropyridine calcium-channel antagonist, facilitates acquisition of the conditioned response in aging rabbits. Although calcium-channel antagonists directly block neuronal calcium currents in vitro, they also alter cerebral blood flow in vivo. Thus, the effects of nimodipine on hippocampal neuronal activity in awake animals were examined, with controls for cerebrovascular changes. A total of 457 pyramidal cells and 160 theta cells were studied. During infusion of nimodipine, pyramidal cell firing activity was enhanced and theta interneuron activity was suppressed at all doses tested in aging animals. This effect was rapidly reversed when infusion of the drug ceased. The greatest enhancement of neuronal firing was seen at the most behaviorally effective dose of nimodipine. The enhancement of pyramidal cell firing was age-dependent with greater increases in firing activity seen in aging than in young animals, but with a similar dose-dependent pattern of effects in the two age groups. Two other calcium-channel antagonists, nifedipine and flunarizine, did not significantly alter spontaneous firing rates of hippocampal neurons. A calcium-channel agonist, BAY-K-8644, produced less easily interpretable results. BAY-K-8644 enhanced interneuron activity at one dose, but enhanced pyramidal cell activity at a dose one log unit higher. The calcium-channel agonist's enhancement of pyramidal cell actvity at highest dose was sustained up to 1 h after drug infusion. Nimodipine's enhancement of the activity of hippocampal pyamidal cells is consistent with the hypothesis that these neurons, which play a necessary role in some forms of learning, may mediate the calcium-channel antagonist's behavioral effects.

Spatial firing properties of hippocampal theta cells

Previous studies have shown that complex-spike cells, the most common cell type recorded in the hippocampus of freely moving rats, have the property of spatial firing--that is, a cell will fire rapidly only when the animal is in a particular part of its environment (O'Keefe and Dostrovsky, 1971). In the current study, we analyze the spatial firing of theta cells, the second major class of cells in the hippocampus, which are thought to correspond to nonpyramidal neurons (Fox and Ranck, 1975, 1981). Our purposes were to extend findings from earlier spatial analyses (McNaughton et al., 1983; Christian and Deadwyler, 1986), and to determine whether the spatial firing is cell specific and independent of behavior. Theta cells were recorded from rats in a cylindrical enclosure using techniques previously used for the analysis of spatial firing in complex-spike cells (Muller et al., 1987). The spatial firing patterns of individual neurons appeared as a complex surface with several regions of high and low firing. The ratio of firing from high- to low-rate regions averaged 2.5. These spatial firing patterns were smooth and reproducible, but less so than for complex-spike cells. When a cue card on the wall was moved, theta cell firing patterns remained in register with the cue. Two analyses were performed to determine whether spatial firing patterns were secondary to spatial distributions of behavior. When only locomotor data segments were selected, spatial variations were more clear-cut. In an attempt to test whether theta cells had cell-specific patterns of firing, pairs of theta cells were recorded simultaneously. On all occasions, the firing distribution for each of the cells in a pair was clearly distinctive. These findings support the conclusions that theta cell activity contains a spatial signal that is cell specific and not secondary to other firing correlates.

Behavioral correlates of theta-on and theta-off cells recorded from hippocampal formation of mature young and aged rats

Most hippocampal formation single units in freely behaving rats fall into one of two categories (Ranck 1973). The most obvious behavioral correlate of complex-spike (CS) cells is spatially selective discharge (O'Keefe and Dostrovsky 1971), while theta cells show increased firing in phase with the EEG theta rhythm associated with Vanderwolf's Type I behaviors (e.g. walking, exploration). Recently, Colom and Bland (1987) described, in urethane anesthetized animals, a class of non-CS cell which was inactive in the presence of EEG theta and discharged continuously during LIA. They called these "theta-off" cells and used the term "theta-on" to refer to the classical "theta" cell. We describe the behavioral correlates of 14 theta-off cells encountered in CA1 (n = 1), hilus fascia dentata (FD; n = 4), subiculum (n = 6), abd entorhinal cortex (n = 3). These cells were encountered very infrequently in the course of several experimental investigations of mature young and old rats involving 885 hippocampal neurons recorded from 33 rats during radial maze performance. Fourteen theta-on cells encountered within a few hundred microns of the sites where theta-off cells were recorded were included for comparison. Both theta-on and theta-off cells discharged single spikes and did not show CS bursting characteristic of pyramidal cells. Theta-off cells, however, exhibited significantly greater spike durations than theta-on cells. Mean rates for theta-on and theta-off cells were 8.7 Hz and 6.5 Hz, respectively. Maximum rates were 114 Hz and 104 Hz, respectively. Some cells of both types showed 6-8 Hz modulation while animals traversed the maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Preserved spatial coding in hippocampal CA1 pyramidal cells during reversible suppression of CA3c output: evidence for pattern completion in hippocampus

Medial septal modulation of hippocampal single-unit activity was examined by assessing the behavioral and physiological consequences of reversibly inactivating the medial septum via microinjection of a local anesthetic (tetracaine) in freely behaving rats trained to solve a working memory problem on a radial maze. Reversible septal inactivation resulted in a dramatic, but temporary (15-20 min), impairment in choice accuracy. In addition, movement-induced theta (theta) modulation of the hippocampal EEG was eliminated. Septal injection of tetracaine also produced a significant reduction in location-specific firing by hilar/CA3c complex-spike cells (about 50%), with no significant change in the place-specific firing properties of CA1 complex-spike units. The mean spontaneous rates of stratum granulosum and CA1 theta cells were temporarily reduced by about 50% following septal injection of tetracaine. Although there was a significant reduction in the activities of inhibitory interneurons (theta cells) in CA1, there was no loss of spatial selectivity in the CA1 pyramidal cell discharge patterns. We interpret these results as support for the proposal originally put forth by Marr (1969, 1971) that hippocampal circuits perform pattern completion on fragmentary input information as a result of a normalization operation carried out by inhibitory interneurons. A second major finding in this study was that location specific firing of CA1 cells can be maintained in the virtual absence of the hippocampal theta-rhythm.

Reversible inactivation of the medial septum: selective effects on the spontaneous unit activity of different hippocampal cell types

The contribution of septal afferents to spontaneous hippocampal single unit activity was examined by reversibly inactivating the medial septal nucleus using microinjections of the local anethetic lidocaine. Septal inactivation reduced spontaneous firing of cells in stratum granulosum and in the hilar/CA3 region for periods of up to about 15 min. The firing rates of CA1 complex-spike (pyramidal) cells, however, were not changed, although CA1 theta cells (inhibitory interneurons) exhibited a significant reduction in spontaneous rate. One interpretation of this pattern of results is that the output of CA1 pyramidal cells is maintained roughly constant in spite of reduced input from CA3 because of a proportional reduction in feedforward inhibition. This interpretation is consistent with Marr's 22 formulation of the manner in which the hippocampus implements distributed associative memory. Alternatively, afferents to CA1 originating from regions other than CA3 may play a larger role in regulating CA1 output than previously assumed.

Fluctuations in spontaneous discharge of hippocampal theta cells during sleep-waking states and PCPA-induced insomnia.

1. The spontaneous activity of hippocampal theta cells in head-restrained cats was recorded during slow-wave sleep (SWS), paradoxical sleep (PS), and the attentive state of bird watching (BW). We also recorded theta cell activity during a state of insomnia with pontogeniculoocipital (PGO) waves, which was induced by the administration of p-chlorophenylalanine (PCPA), a selective inhibitor of serotonin synthesis. 2. The time-dependent structure of fluctuations in theta cell activity was evaluated by power spectral analysis and Markovian analysis. The coefficient of variation for these time series was used as a measure of the variability of theta cell activity, which indicates the relative amplitude of fluctuations. 3. During SWS, theta cell activity showed a larger variability and a flat spectrum, i.e., low Markovian properties. During PS, this activity exhibited smaller variability and high spectral density in a low-frequency band (0.01-1.0 Hz), i.e., high Markovian properties. During BW, variability, spectral and Markovian properties were intermediate. 4. The firing pattern of theta cells during PCPA-induced insomnia was similar to that during PS. However, after the administration of either a serotonin agonist, 5-Methoxy-N,N-dimethyltryptamine, or a choline antagonist, atropine sulfate, theta cell activity no longer exhibited PS-like fluctuations, revealing instead a firing pattern similar to that during SWS. 5. During PS and PCPA-induced insomnia, not only the unit activity of theta cells, but PGO activity and theta wave frequency exhibited slow fluctuations, i.e., the high spectral density in the low-frequency band (0.01-1.0 Hz). 6. Cross-correlation analyses were performed between the fluctuations in theta cell activity, theta wave frequency, and PGO activity. These fluctuations correlated with each other during both PS and PCPA-induced insomnia. Bursts of PGO waves especially contributed to these cross-correlations. 7. These results suggest, first, that the slow fluctuations of the theta cell activity during PS and PCPA-induced insomnia is the physiological expression of the removal of aminergic influences and, secondly, that they are dependent on cholinergic mechanisms, including PGO generators.

Cue-sampling and goal-approach correlates of hippocampal unit activity in rats performing an odor-discrimination task

Several techniques previously used to describe behavioral correlates of hippocampal unit and slow-wave activity are combined in a single odor-discrimination paradigm. Rats repetitively performed a sequence of behaviors during each trial: approach to a stimulus-sampling port, investigatory sniffing of the odor cue, orientation and approach toward a separate reward location, and water reward consumption. In a series of post hoc analyses, spike activity was time-locked to variations of each task event to uncover behavioral and physiological parameters that best synchronized unit firing. Three major categories of cells were identified: (1) "Cue-sampling" cells fired after onset of odor-cue sampling. Response magnitude was related to cue valence on both the current and past trials. (2) "Goal-approach" cells fired prior to arrival at either the odor-sampling port or reward cup. A number of sampling and approach cells also had place correlates. However, detailed analyses indicated that specific behaviors associated with increased firing reliably occurred at the same place. Unit activity was at least as well described by behavioral as spatial parameters. (3) "Theta" cells fired at high rates in strict relation to the ongoing limbic theta rhythm. This categorization suggests a functional organization of the hippocampus in which different cell types play complementary roles. Cue-sampling cells activated by discriminative stimuli during attentive fixations may be involved in comparing relative cue valence. Goal-approach cells may be involved in orientation movements for successive cue-sampling periods. Theta cells may provide synchronization of sensory acquisition during sampling, as well as in orientation movements during approach.

Medial septal modulation of hippocampal theta cell discharges

The effect of small electrolytic lesions in various areas of the septum on the behavioral correlates and firing repertoires of hippocampal theta cells, was investigated in the freely moving rabbit. Lesions localized to the medial septum were found to abolish both slow wave theta and the rhythmic firing of CA1 and dentate layer theta cells, in both the type 1 theta (movement) and type 2 theta (sensory processing) behavior conditions. Small lesions of the diagonal band, lateral septum and fimbria/fornix regions only affected rhythmicity to the extent that they also involved the medial septal region. The same medial septal lesions that abolished rhythmicity were also shown to reduce the mean discharge rate of theta cells occurring during the type 1 movement condition by approximately 50%, while the discharge rate occurring during the type 2 sensory processing condition did not change significantly. Behavioral changes were also only observed for lesions involving the medial septum. The importance of afferent input from the medial septum in the generation of hippocampal theta cell rhythmicity was discussed.

Interactions of phencyclidine with hippocampal circuitry: Evidence for neuronal heterogeneity

The discovery of phencyclidine (PCP) receptors has stimulated the search for specific PCP antagonists. A direct product of this research is metaphit, an irreversible PCP ligand, which has recently been synthesized. In this study we examined the effects of metaphit on the responses of hippocampal neurons to PCP. On the basis of unfiltered action potential durations, hippocampal cells were divided into two groups, complex-spike cells and theta neurons. Local application of PCP caused inhibitions of the spontaneous firing rates of complex-spike cells. Metaphit, locally applied, antagonized approximately 50% of these responses, while the remaining responses were unaffected. In contrast, PCP caused increases in the spontaneous firing rates of theta cells and in almost all cases, these responses to PCP were attenuated by metaphit administration. These effects of metaphit were specific for PCP as the responses to locally applied norepinephrine were not altered by metaphit. The data suggest two mechanisms of action of PCP in the hippocampus. In addition, these mechanisms may be localized in part to different cell types.