Biomedical subjects

S E Fox

Publications and source records attributed to S E Fox.

At least 19 recordsLinked to original sources

PubMed2003

Muscarinic blockade slows and degrades the location-specific firing of hippocampal pyramidal cells.

The firing of rat hippocampal pyramidal cells is determined both by the animal's location and by the state of the hippocampal EEG. Because cholinergic transmission plays a role in EEG activity, we expected that its modification would alter place cell activity. We therefore investigated the effects on place cell activity of blocking muscarinic transmission with intracerebroventricular injections of scopolamine. Scopolamine reduced both the rate of place cell discharge inside firing fields and the spatial coherence of the fields; discharge outside of the fields also showed small increases. After injections, fields were shifted farther from their previous location than for saline controls, indicating reduced reproducibility after muscarinic blockade. Scopolamine increased the time rats were stationary, but changes in place cell activity persisted even after analysis was restricted to periods of walking, suggesting that the behavioral changes cannot account for the cell discharge changes. The scopolamine effects were dose dependent to an extent that varied between different measures. The firing rates of interneurons showed only a minor trend to decrease after scopolamine. Nevertheless, the spatial coherence of interneuron firing patterns was reduced, consistent with the recent demonstration that their positional firing is mediated by the location-specific firing of pyramids (Marshall et al., 2002). These results demonstrate that acetylcholine enhances positional firing patterns in the hippocampus. Muscarinic blockade weakens the positional firing of most place cells and therefore renders them less useful for precise representation of the environment. This effect may underlie the difficulties in spatial learning and problem solving caused by abnormalities of cholinergic transmission.

Acetylcholine↗

PubMed1999

Action potentials and relations to the theta rhythm of medial septal neurons in vivo.

The influence of the medial septal nucleus and the nucleus of the diagonal band of Broca (MS-DB) on the hippocampal theta rhythm includes both cholinergic and gamma-aminobutyric acid (GABAergic) components. To understand the intrinsic septal interactions and the separate contributions of the cholinergic and GABAergic septohippocampal neurons to the theta rhythm in behaving animals, it is essential to be able to identify these two classes from extracellular recordings. Here the durations of extracellularly recorded action potentials are compared with the other characteristics of the neurons. Extracellular recordings were taken from neurons of the MS-DB both in freely moving rats (114 cells) and in urethane-anesthetized rats (112 cells). These were compared with intracellular recordings taken from MS-DB neurons in urethane-anesthetized rats (58 cells). Hippocampal EEG was recorded from above the CA1 pyramidal cell layer (CAI theta) and near the hippocampal fissure (dentate theta) to compare the firing phase across cells. Here it is shown that two major types of rhythmically bursting cells in the MS-DB that had been distinguished previously in intracellular recordings in vivo are also separable in extracellular recordings in vivo on the basis of the durations of their action potentials. In both awake and anesthetized rats the main properties of the two cell types were found to differ: firing rate, phase-relation to the hippocampal theta rhythm and sensitivity of their rhythmicity to blockade of muscarinic transmission. As was previously shown for intracellular recordings in anesthetized rats, it is shown here that in awake rats, too, the more rapidly firing brief-spike (putative GABAergic) cells fired with highest probability on the negative phase of the dentate theta, whereas the more slowly firing long-spike (putative cholinergic) cells fired mostly on the positive phase. Previous work showed that in intracellular recordings from anesthetized rats the rhythmic firing of most brief-spike cells was still retained even during muscarinic blockade, but that of most long-spike cells was lost. Here we also report a recategorization according to spike duration of existing extracellular recordings taken from anesthetized rats, confirming the above observation with much larger numbers of cells. Three additional major new findings are also reported here. (1) In awake rats, muscarinic blockade has relatively little effect on either cell type. (2) Under anesthesia, the firing rates of both cell types are lower than in awake rats, but the effect is greater on the long-spike cells, where the anesthesia also reduces the rhythmicity of the cell firing. (3) Rhythmicity of the putative GABAergic cells is also retained after local injection of GABA-A antagonist, whereas that of the putative cholinergic cells is eliminated. We conclude that either systemic muscarinic blockade or urethane anesthesia alone have relatively little effect on neurons in the defined above MS-DB, but a combination of the two has profound effects on the rhythmicity of the cholinergic cells, largely sparing the GABA-ergic cells. Taken together, the results suggest that generation of theta rhythm requires a background of excitatory influences on the hippocampus (that can be maintained by either muscarinic or glutamatergic inputs) in combination with the phasic disinhibitory action mediated by the GABAergic MS-DB projection. They also provide additional support for the notion that the phasic activity in local collaterals of GABAergic MS-DB cells contributes to the phasic modulation of the firing of cholinergic septohippocampal neurons.

Action Potentials↗

PubMed1998

Application of the combined single-cell recording/intracerebral microdialysis method to alcohol research in freely behaving animals.

Intercellular communication in brain is coded in neuronal firing patterns, determined by the interplay of intra- and extracellular molecular systems. It is not clear how ethanol perturbs this molecular interplay in the motivational, emotional, and cognitive neural networks in brain to induce those specific, aberrant, cell-firing patterns that lead to craving for alcohol, excessive alcohol consumption, and impaired cognition. However, resolution of this problem is essential to an understanding of the basic mechanisms of alcohol-related disorders and to develop effective therapies for their treatment. It is difficult to obtain information on the molecular background of cell-firing regulation in brain during behavioral events. We have recently developed a new in vivo method, combined single-cell recording/intracerebral microdialysis in freely behaving animals, which has the ability to extract such information from brain. The principal feature of the technique is that it records the firing of single neurons in discrete brain sites and deliver drugs, alone or in combinations, via microdialysis, into the extracellular environment of the recorded cells, while the experimental animal is behaving freely. Accordingly, the method allows the determination of drug actions on cellular firing within distinct neural circuits during normal and abnormal behaviors. Thus, it can provide insights into the physiological or pathophysiological molecular machinery of the examined cells. The present paper describes this method, demonstrates how administration of ethanol via intrahippocampal microdialysis affects the firing of hippocampal place cells, and discusses the potential of the technique in future alcohol research.

Animals↗

PubMed1998

The outreach-assisted model of partner notification with IDUs.

OBJECTIVE: This analysis describes the Outreach-Assisted Model of Partner Notification, an innovative strategy for encouraging seropositive injecting drug users (IDUs) to inform their partners of shared human immunodeficiency virus (HIV) exposure. The analysis focuses on two core components of the notification process: the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus. METHODS: Using community outreach techniques, 386 IDUs were recruited for HIV pretest counseling, testing, and partner notification over a 12-month period. Of these, 63 tested HIV seropositive, and all but three returned for their test results. The 60 who were informed of their serostatus were randomly assigned to either a minimal or an enhanced intervention condition. Participants assigned to the minimal (self-tell) group were strongly encouraged to inform their partners of possible exposure. Those assigned to the enhanced (outreach-assisted) group had the option of either informing one or more of their partner(s) themselves or choosing to have the project's outreach team do so. RESULTS: Together, the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years. By itself, drug use accounted for half of all partners named. Sexual behavior alone accounted for 25% of named partners. Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner; the team was requested to notify 71% of the total number of partners whom this group named. CONCLUSIONS: Findings suggest that IDUs want to notify their partners of shared HIV exposure. Outreach assistance was the preferred mode in the majority of cases. Expanding traditional community-based HIV outreach activities to include delivering street-based counseling, test, a partner notification appears to be a positive and workable prevention strategy.

Adult↗

PubMed1997

Intracellular recordings from medial septal neurons during hippocampal theta rhythm.

The electrophysiological properties of neurons of the medial septal nucleus and the nucleus of the diagnonal band of Broca (MS/DB) were studied using intracellular methods in urethane-anesthetized rats. Three types of rhythmically bursting neurons were identified in vivo on the basis of their action potential shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics, firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%) had high firing rates and extremely reliable bursts with 6-16 spikes per theta cycle, which were highly resistant to scopolamine action. (2) Cells with short-duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%) also had high firing rates and reliable bursts with 4-13 spikes per theta cycle, phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing current injection revealed a brief membrane time constant, time-dependent membrane rectification and a burst of firing at the break. Depolarizing current steps produced high-frequency repetitive trains of action potentials without spike frequency adaptation. The action potential and membrane and characteristics of this cell type are consistent with those described for GABAergic septal neurons. Many of these neurons retained their theta-bursting pattern in the presence of muscarinic antagonist. (3) Cells with long-duration action potentials and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and usually only 1-3 spikes per theta cycle, locked mainly to the positive peak of the dentate theta rhythm. Hyperpolarizing current injection revealed a long membrane time constant and a break potential; a depolarizing pulse caused a train of action potentials with pronounced spike frequency adaptation. The action potential and membrane properties of this cell type are consistent with those reported for cholinergic septal neurons. The theta-related rhythmicity of this cell type was abolished by muscarinic antagonists. The phasic inhibition of "cholinergic" MS/DB neurons by "GABAergic" MS/DB neurons, followed by a rebound of their firing, is proposed as a mechanism contributing to recruitment of the whole MS/DB neuronal population into the synchronized rhythmic bursting pattern of activity that underlies the occurrence of the hippocampal theta rhythm.

Action Potentials↗

PubMed1996

Manipulation of pyramidal cell firing in the hippocampus of freely behaving rats by local application of K+ via microdialysis.

In this study, microdialysis was performed in the hippocampus of freely behaving rats, and the firing of pyramidal cells, including place cells, was recorded at the site of the microdialysis probe. For 10-min periods, the artificial cerebrospinal fluid (ACSF) in the microdialysis system was replaced with ACSF containing 50 mM K+ (high K+ solution). Complementary in vitro tests determined that microdialysis with such high K+ solution produced an outflow of 5% of the perfused K+ from the microdialysis probe. Application of K+ with this method into the CA1 region significantly increased the firing of the local pyramidal cells, including place cells, during both movement and sleep. On average, K+ exposures increased the firing rate of the neurons to 306% and 448% of the control firing rate during movement and sleep, respectively. After the termination of the K+ outflow, the cells continued to discharge for 5-30 min with a significantly higher frequency than before the K+ challenge. This phenomenon also occurred in both behavioral states. During the period of enhanced firing, the out-of-field firing rate of the recorded place cells was dramatically increased. It was also found that during the K+ applications, otherwise silent pyramidal cells often became electrically active. The K(+)-induced firing modifications were usually not accompanied by behavioral or EEG changes. The data raise the possibility that transient elevations in the extracellular K+ concentration contribute to the ionic/molecular processes which are responsible for plastic firing pattern modifications in hippocampus. Pharmacological manipulation of place cells with the described method offers a new strategy to understand the molecular bases of spatial memory.

Animals↗

PubMed1994

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 network. Such studies will provide new insights into the molecular basis of neuronal activity in the brain in the context of behavior, including learning.

Animals↗

PubMed1993

Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators.

Single-electrode depth profiles of the hippocampal EEG were made in urethane-anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC'-CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta-related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated.

Action Potentials↗

PubMed1993

The mere exposure effect for stimuli presented below recognition threshold: a failure to replicate.

Repeated exposure to a stimulus increases one's affect toward that stimulus. This finding, termed the mere exposure effect, has been obtained even when the exposure durations are below the threshold of recognition. Reported are three experiments designed to assess whether the mere exposure effect for stimuli presented below the threshold of recognition could be obtained for meaningful stimuli. Analysis showed that meaningfulness of the stimuli had no effect on ratings of affect; however, we did not replicate previous findings of a mere exposure effect for stimuli that were not recognized. The robustness of the mere exposure effect for stimuli presented below the threshold of awareness was questioned.

Adult↗

PubMed1992

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

The medial septal nuclei are essential for the naturally occurring 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 antimuscarinic 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 excitatory collaterals of pyramidal cells; and (2) somatic burst firing by CA1 pyramidal cells requires the presence of acetylcholine.

Acetylcholine↗

PubMed1992

Hippocampal laminar glucose utilization and theta rhythm following unilateral fimbria-fornix lesions in rats.

Laminar profiles of glucose utilization were related to the presence or absence of movement-related hippocampal theta rhythm in CA1 and dentate gyrus of rats after aspirative unilateral combined lesions of the fimbria-fornix and cingulum. Three groups were studied: (1) sham-operated rats, (2a) lesioned rats with an ipsilateral loss of theta activity at 4 weeks post-lesion that persisted at 12 weeks post-lesion, and (2b) lesioned rats with a loss of theta activity at 4 weeks post-lesion, but a recovery of theta rhythm at 12 weeks post-lesion. Fimbria-fornix/cingulum lesions served both to abolish ipsilateral theta rhythm and to decrease ipsilateral glucose metabolism in all cell layers of CA1 and the dentate gyrus, when normalized to the contralateral hemisphere. Although glucose metabolism in lesioned animals with a recovery of theta rhythm was not as high as control levels, in several laminae it was significantly higher than that of lesioned animals with persistent loss of theta rhythm. These laminae included the dentate hilus and strata oriens, pyramidale and lacunosum-moleculare of CA1. The increased glucose metabolism associated with the return of theta rhythm suggests a functional reinnervation of these layers of the hippocampus in such animals.

Afferent Pathways↗

PubMed1992

Firing relations of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats.

The firing of neurons from layers II and III of medial entorhinal cortex (MEC) was examined in relation to the hippocampal theta rhythm in urethane anesthetized and walking rats. 1) MEC neurons showed a significant phase relation to the hippocampal theta rhythm in both walking and urethane anesthetized rats, suggesting that this region contributes to the generation of both atropine-resistant and atropine-sensitive theta rhythm components. 2) The proportion of phase-locked cells was three times greater in walking rats (22/23 cells) as compared to anesthetized rats (8/23 cells), indicating that MEC cells made a greater contribution during walking theta rhythm. This difference was also manifest in the greater mean vector length for the group of phase-locked MEC cells during walking: 0.39 +/- 0.13 versus 0.21 +/- 0.08. Firing rate differences between walking and urethane conditions were not significant. 3) In walking rats, MEC cells fired on the positive peak of the dentate theta rhythm (group mean phase = 5 degrees; 0 degrees = positive peak at the hippocampal fissure). This is close to the reported phases for dentate granule and hippocampal pyramidal cells. The distribution of MEC cell phases in urethane anesthetized rats was broader (group mean phase = 90 degrees), consistent with the phase data reported for hippocampal projection cells. These findings suggest that medial entorhinal neurons are the principal determinant of theta-related firing of hippocampal neurons and that their robust rhythmicity in walking as compared to urethane anesthesia accounts for EEG differences across the two conditions.

Anesthesia↗

PubMed1991

Hippocampal theta activity in monkeys.

The hippocampal theta rhythm has been extensively studied in many subprimate mammals. Considering the technical difficulties involved in recording from freely moving animals during voluntary motion and REM sleep, it was thought that urethane anesthesia might be appropriate for initial studies of the primate hippocampal EEG. Three of three macaques and one of two squirrel monkeys showed clear rhythmic hippocampal EEG activity. One very old squirrel monkey (a 16-year-old female) showed no theta activity in the hippocampal EEG. Similarities of the monkey theta activity with theta rhythm of urethane-anesthetized rats included: (1) a high coherence between recordings from electrodes separated by several millimeters within the hippocampal formation; (2) sensitivity of the theta activity to muscarinic drugs; and (3) its correlation with spontaneous movements during light anesthesia. Important differences were: (1) the frequency of the monkey theta activity was 7-9 Hz compared to the 4-5 Hz found in rats; (2) theta activity was not detected in the distal apical dendritic regions of CA1 or dentate in the monkey; (3) considerable amounts of low-frequency EEG co-existed with the monkey theta activity; and (4) the durations of bouts of theta activity in monkeys were much shorter than in rats. We conclude that primates generate hippocampal theta activity homologous, but not identical, to that of rats.

Animals↗

PubMed1991

The propagation potential. An axonal response with implications for scalp-recorded EEG.

An electrophysiological response of axons, referred to as the "propagation potential," was investigated. The propagation potential is a sustained voltage that lasts as long as an action potential propagates between two widely spaced electrodes. The sign of the potential depends on the direction of action potential propagation. The electrode towards which the action potential is propagating is positive with respect to the electrode from which it is receding. For normal frog sciatic nerves the magnitude of the propagation potential was 17% of the peak of the extracellular action potential; TEA increased it to 32%. For normal earthworm median or lateral giant fibers it was 30%. A ripple pattern on the propagation potential was attributed to variation in resistance along the length of the worm. Cooling increased the duration of the propagation potential and attenuated the higher frequency components of the ripple pattern. Differential records from two widely spaced intracellular microelectrodes in the same axon differed from the propagation potential. The amplitude of the plateau relative to the peak was smaller, it decreased as the action potential propagated from one electrode site to the other, and the potential did not return to zero as rapidly as for extracellular records. When propagation was blocked by heat, the propagation potential slowly decayed. There was no ripple pattern during the decay. In a volume conductor, electrodes contacting the worm did not show the typical propagation potential, but electrodes located a few centimeters away from the worm did. Simple core-conductor models based on classical action potential theory did not reproduce the propagation potential. More complex, modified core-conductor models were needed to accurately simulate it. The results suggest that long, slowly conducting fibers can contribute to the scalp-recorded EEG.

Animals↗

PubMed1990

Firing relations of lateral septal neurons to the hippocampal theta rhythm in urethane anesthetized rats.

The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5 +/- 9.9 spks/sec; non-theta: 6.0 +/- 5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed.

Action Potentials↗

PubMed1990

Do septal neurons pace the hippocampal theta rhythm?

The hippocampal theta rhythm (rhythmical slow activity, RSA) is one of the most thoroughly studied EEG phenomena. Much of this experimental interest has been stimulated by suggestions that the mnemonic functions of the hippocampus may depend upon theta-related neuronal activity. Inputs from the medial septal nuclei to the hippocampus were shown to be essential for the theta rhythm in the 1950s, but the role of these basal forebrain projections has not been clearly defined. Four models of the septo-hippocampal connections involved in theta rhythm production are reviewed as the precise roles of these projections are discussed. In our final, consolidated model both cholinergic and GABAergic septal projection cells fire in rhythmic bursts that entrain hippocampal interneurons. The resulting rhythmic inhibition of hippocampal projection cells, together with their excitatory interconnections, generates at least one component of the theta rhythm.

Action Potentials↗

PubMed1989

Detection of an atropine-resistant component of the hippocampal theta rhythm in urethane-anesthetized rats.

An important pharmacological feature of the hippocampal theta rhythm in urethane-anesthetized animals is its apparent sensitivity to antimuscarinic drugs. This sensitivity may be partly due to a masking of the theta frequency by increases in both higher and lower frequency EEG components that are unrelated to any residual theta rhythm. The discovery of atropine-resistant, rhythmic medial septal neurons has provided a physiological trigger for averaging EEG and unit activity after large atropine doses. Such averaging has permitted the detection of an atropine-resistant component of the hippocampal theta rhythm in urethane-anesthetized rats. The postatropine theta activity recorded from both CAl (superficial to the pyramidal cell layer) and dentate (near the hippocampal fissure) in 15 rats was typically reduced in amplitude, but the recordings from the two locations maintained their phase relations to the septal units and to each other. The presence of this residual theta component after doses as large as 100 mg/kg indicates that it cannot be mediated by muscarinic cholinergic receptors. The coupling of the signal to the atropine-resistant septal cells strengthens our previous suggestion that these septo-hippocampal neurons are not cholinergic, and are therefore probably GABAergic.

Anesthesia↗

PubMed1989

Firing relations of medial septal neurons to the hippocampal theta rhythm in urethane anesthetized rats.

On the basis of spontaneous firing patterns and relations to the hippocampal theta rhythm, three cell types were identified within the medial septal nucleus and vertical limb of the nucleus of the diagonal band of Broca (MSN-NDB). In addition to the well known rhythmically bursting cells that fired in bursts on each cycle of the hippocampal theta rhythm, two other cell types are distinguished. "Clock" cells fired at high rates with a very regular, periodic firing pattern that was unrelated to the theta rhythm. "Irregular" cells fired at much lower rates, especially during theta rhythm, and had a pseudo-random firing pattern. The firing of "irregular" cells was often significantly phase-locked to the hippocampal theta rhythm. Crude estimates of the relative proportions of these cell types suggest that the rhythmically bursting cells comprise about 75% of the cells of the MSN-NDB. These three cell types bear a remarkable resemblance, in firing patterns and relative proportions, to the three principal cell types of the medial septal nuclei described in the freely moving rat (Ranck 1976). Measurements of the preferred phases of firing of 128 rhythmically bursting septal neurons (including 22 atropine-resistant and 11 atropine-sensitive cells) indicate that there is no single preferred phase of firing for the population. Rather the distribution of phases over the theta cycle is statistically flat. Variations in recording locations cannot account for this distribution since large differences in preferred phase were found for pairs of cells at the same location. Similarly, plotting only the group of cells identified as projection cells by antidromic activation from the fimbria/fornix, failed to reveal a peak in the distribution. In contrast to the rhythmically bursting cells, the distribution of preferred firing phases for the "irregular" cells with a significant phase-locking to the theta rhythm did have a clear peak. The peak occurred near the dentate theta rhythm positivity, consistent with the hypothesis that they are driven by feedback from CA1 complex-spike cells.

Action Potentials↗