Large Amplitude Irregular Activity Research Articles

Chaotic dynamics as a mechanism of rapid transition of hippocampal local field activity between theta and non-theta states.

We propose a dynamical model of the local hippocampal circuit realizing the transition between the theta and non-theta states. We model the interaction between hippocampal local rhythm generators and the external periodic input from the medial septum and diagonal band of Broca (MS-DBB). With our model, bifurcation of the nonlinear dynamics serves as a mechanism that realizes two distinctive oscillations in the hippocampus, where the amplitude of the oscillatory input from the MS-DBB works as a bifurcation parameter. We model the network of the hippocampal interneurons with a network of simple class 1 neuron models connected mutually with gap junctions. The model neurons exhibit highly synchronous periodic oscillations under the existence of an external force from the MS-DBB, just as the real hippocampus shows theta oscillation under the rhythmic input from the MS-DBB. The model shows diffusion-induced chaotic dynamics under an aperiodic MS-DBB activity, just as the large amplitude irregular activity appears following the disappearance of the rhythmicity of the MS-DBB neurons in the real brain. The model is consistent with both previous experimental findings reporting the existence of local rhythm generators in the hippocampus and the executive role of the MS-DBB in synchronizing theta oscillation in vivo. Our model also replicates the traveling waves of theta oscillations in two-dimensionally coupled networks.

GABAergic Neurons of the Medial Septum Lead the Hippocampal Network during Theta Activity

Information processing in the hippocampus critically relies on its reciprocal interaction with the medial septum (MS). Synchronization of the septo-hippocampal system was demonstrated during both major hippocampal activity states, the regular theta rhythm and the large amplitude irregular activity. Previous experimental and modeling data suggest that the MS provides rhythmic drive to the hippocampus, and hippocampo-septal feedback synchronizes septal pacemaker units. However, this view has recently been questioned based on the possibility of intrahippocampal theta genesis. Previously, we identified putative pacemaker neurons expressing parvalbumin (PV) and/or the pacemaker hyperpolarization-activated and cyclic nucleotide-gated nonselective cation channel (HCN) in the MS. In this study, by analyzing the temporal relationship of activity between the PV/HCN-containing medial septal neurons and hippocampal local field potential, we aimed to uncover whether the sequence of events during theta formation supports the classic view of septal drive or the challenging theory of hippocampal pacing of theta. Importantly, by implementing a circular statistical method, a temporal lead of these septal neurons over the hippocampus was observed on the course of theta synchronization. Moreover, the activity of putative hippocampal interneurons also preceded hippocampal local field theta, but by a shorter time period compared with PV/HCN-containing septal neurons. Using the concept of mutual information, the action potential series of PV/HCN-containing neurons shared higher amount of information with hippocampal field oscillation than PV/HCN-immunonegative cells. Thus, a pacemaker neuron population of the MS leads hippocampal activity, presumably via the synchronization of hippocampal interneurons.

Behavioral state-dependent episodic representations in rat CA1 neuronal activity during spatial alternation

Hippocampus is considered crucial for episodic memory, as confirmed by recent findings of "episode-dependent place cells" in rodent studies, and is known to show differential activity between active exploration and quiet immobility. Most place-cell studies have focused on active periods, so the hippocampal involvement in episodic representations is less well understood. Here, we draw a typology of episode-dependent hippocampal activity among three behavioral periods, presumably governed by different molecular mechanisms: Active exploration with type 1 theta, quiet alertness with type 2 theta, and consummation with large amplitude irregular activity. Five rats were trained to perform a delayed spatial alternation task with a nose-poke paradigm and 12 tetrodes were implanted for single-unit recordings. We obtained 135 CA1 pyramidal cells and found that 75 of these fired mainly during active exploration, whereas 42 fired mainly during quiet alertness and 18 during consummation. In each type of neuron, we found episode-dependent activity: 51/75, 22/42, and 15/18, respectively. These findings extend our knowledge on the hippocampal involvement in episodic memory: Episode dependency also exists during immobile periods, and functionally dissociated cell assemblies are engaged in the maintenance of episodic information throughout different events in a task sequence.

To move or not: Previous experience in a runway avoidance task determines the appearance of hippocampal Type 2 sensory processing theta

Rats in a runway avoidance task responded to a test shock probe with a period of immobility lasting from 2 to 6 s. The shock avoidance-trained group displayed hippocampal theta during the immobility response. The inescapable shock group, in contrast, displayed large amplitude irregular activity (LIA). Following reversal training to escapable shock, all shock avoidance-trained rats responded with LIA and inescapable shock trained rats, reversed to shock avoidance, displayed theta.

Hippocampal Slow Oscillation: A Novel EEG State and Its Coordination with Ongoing Neocortical Activity

State-dependent EEG in the hippocampus (HPC) has traditionally been divided into two activity patterns: theta, a large-amplitude, regular oscillation with a bandwidth of 3-12 Hz, and large-amplitude irregular activity (LIA), a less regular signal with broadband characteristics. Both of these activity patterns have been linked to the memory functions subserved by the HPC. Here we describe, using extracellular field recording techniques in naturally sleeping and urethane-anesthetized rats, a novel state present during deactivated stages of sleep and anesthesia that is characterized by a prominent large-amplitude and slow frequency (< or =1 Hz) rhythm. We have called this activity the hippocampal slow oscillation (SO) because of its similarity and correspondence with the previously described neocortical SO. Almost all hippocampal units recorded exhibited differential spiking behavior during the SO as compared with other states. Although the hippocampal SO occurred in situations similar to the neocortical SO, it demonstrated some independence in its initiation, coordination, and coherence. The SO was abolished by sensory stimulation or cholinergic agonism and was enhanced by increasing anesthetic depth or muscarinic receptor antagonism. Laminar profile analyses of the SO showed a phase shift and prominent current sink-source alternations in stratum lacunosum-moleculare of CA1. This, along with correlated slow oscillatory field and multiunit activity in superficial entorhinal cortex suggests that the hippocampal SO may be coordinated with slow neocortical activity through input arriving via the temporo-ammonic pathway. This novel state may present a favorable milieu for synchronization-dependent synaptic plasticity within and between hippocampal and neocortical ensembles.

Functional connectivity between the red nucleus and the hippocampus supports the role of hippocampal formation in sensorimotor integration.

Experiments were carried out in urethane-anesthetized rats to evaluate the hypothesis that the red nucleus has functional connections with the hippocampal formation. Depth profiles of electrical stimulation in experiment 1 confirmed that stimulation administered to the red nucleus elicited theta field activity in the hippocampal formation with a linear relationship between stimulus intensity and theta frequency. Experiment 2 showed that microinfusion of local anesthetic procaine hydrochloride into the medial septum resulted in a reversible blockade of theta field activity elicited by electrical stimulation of the red nucleus. In experiment 3, the discharge activity of red nucleus cells was recorded during the field conditions of hippocampal synchrony (theta) and hippocampal asynchrony [large amplitude irregular activity (LIA)]. Analysis revealed that 26/46 (56%) of red nucleus cells were theta-related, whereas the remaining 20 (44%) were nonrelated. The majority of theta-related cells were classified as tonic theta-on. A brief increase above the basal discharge rate of tonic theta-on red nucleus cells during LIA predicted the transition from LIA to theta with 400- to 500-ms latency. Furthermore, higher frequency transitional discharges predicted higher theta frequencies, whereas higher discharge rates during theta predicted shifts to higher theta frequencies. The results supported the conclusion that the red nucleus, traditionally associated with motor functions, is functionally connected with the neural circuitry involved in the generation of theta band oscillation and synchrony in the hippocampal formation, in agreement with the predictions of the sensorimotor integration model of hippocampal function.

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.

Relationship between membrane potential oscillations and rhythmic discharges in identified hippocampal theta-related cells.

Intracellular recordings of cells, classified according to the criteria of Colom and Bland as phasic theta-ON or phasic theta-OFF cells, were carried out in the dorsal region of the hippocampal formation in urethan-anesthetized rats. Cells were studied during two spontaneously occurring hippocampal field conditions, asynchrony, termed large-amplitude irregular activity, and synchrony, termed theta. During the spontaneous cycling between these two field states, the effect of four levels of intracellular depolarizing and hyperpolarizing constant current injections on the amplitude and phase of membrane potential oscillations (MPOs) and the rate and pattern of cell discharges was assessed. Labeled CA1 pyramidal cells and bistratified cells met the criteria for classification as phasic theta-ON cells and labeled CA1 pyramidal layer basket cells, mossy hilar cells, and granule cells met the criteria for classification as phasic theta-OFF cells. MPOs were recorded in CA1 pyramidal cells, CA1 layer basket cells, mossy interneurons, and granule cells only during theta field activity, their onset in theta-ON cells signaled by a depolarizing shift of 5-10 mV and in theta-OFF cells by a hyperpolarizing shift of 5-10 mV, in membrane potential. The effect of current injections in phasic theta-ON and theta-OFF cells during the theta field condition revealed that MPO amplitude was voltage dependent and frequency was voltage independent. There were no phase changes observed in phasic theta-ON cells during current injections; however, amplitude analysis revealed an inverted U-shaped curve asymmetrically distributed around the average value of the membrane potential occurring during the spontaneous theta (no current) control condition. The occurrence and rate of rhythmical cell discharges in CA1 pyramidal phasic theta-ON cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately -57 to -68 mV, corresponding to a range of MPO amplitudes of approximately 4-7 mV. Outside the critical range, rhythmic cell discharges were abolished. Membrane potential oscillations in CA1 pyramidal layer basket cells underwent an approximate 180 degrees phase reversal when the membrane potential was depolarized above -65 mV. The occurrence and rate of rhythmic cell discharges in CA1 pyramidal layer basket cell phasic theta-OFF cells during the theta condition was precisely controlled within a critical range of membrane potential values from approximately -62 to -60 mV, corresponding to a range of MPO amplitudes of approximately 7-7.5 mV. Outside the critical range, cell discharges were absent or occurred singly.

Effect of halothane on type 2 immobility-related hippocampal theta field activity and theta-on/theta-off cell discharges.

Rats were studied in acute and chronic (freely moving) recording conditions during exposure to different levels of the volatile anesthetic halothane, in order to assess effects on hippocampal theta field activity in the chronic condition and on theta-related cellular discharges in the acute condition. Previous work has shown that the generation of hippocampal type 2 theta depends on the coactivation of cholinergic and GABAergic inputs from the medial septum. Based on these data and recent findings that halothane acts on interneuron GABA(A) receptors, we predicted that exposure of rats to subanesthetic levels would result in the induction of type 2 theta field activity. In the chronic condition, exposure to subanesthetic levels of halothane (0.5-1.0 vol %) was found to induce theta field activity during periods of immobility (type 2 theta) with a mean increase of 39% in amplitude (mV) compared to control levels during movement. The total percentage of signal power (V2) associated with peak theta frequencies (80% compared to control levels of 47%) was also increased by halothane. Over the whole range of administered halothane concentrations, theta field frequency progressively declined from a mean peak frequency of 6.5 +/- 0.8 Hz at 0.5 vol % halothane to a mean peak frequency of 4.0 +/- 1.8 Hz at 2.0 vol % halothane. Subsequent administration of a muscarinic cholinergic antagonist, atropine sulfate, selectively abolished all type 2 immobility-related theta field activity, while type 1 movement-related theta was still intact. At anesthetic levels (1.5-2.0 vol %) in acute experiments, hippocampal field activity spontaneously cycled between theta and large-amplitude irregular activity. Analysis of depth profiles in four experiments revealed they were identical to those previously described for rats under urethane anesthesia conditions. In addition, the discharge properties of 31 theta-related cells, classified as tonic and phasic theta-on and tonic and phasic theta-off cells, did not differ significantly from those described previously in rats anesthetized with urethane. These data provide further support for an involvement of GABA(A) receptors in the generation of hippocampal theta.

Hippocampal Population Activity during the Small-Amplitude Irregular Activity State in the Rat

The sleeping rat cycles between two well-characterized physiological states, slow-wave sleep (SWS) and rapid-eye-movement sleep (REM), often identified by the presence of large-amplitude irregular activity (LIA) and theta activity, respectively, in the hippocampal EEG. Inspection of the activity of ensembles of hippocampal CA1 complex-spike cells along with the EEG reveals the presence of a third physiological state within SWS. We characterize the hippocampal EEG and population activity of this third state relative to theta activity and LIA, its incidence relative to REM and LIA, and the functional correlates of its population activity. This state occurs repeatedly within stretches of SWS, occupying approximately 33% of SWS and approximately 20% of total sleep, and it follows nearly every REM episode; however, it never occurs just before a REM episode. The EEG during this state becomes low in amplitude for a few seconds, probably corresponding to "small-amplitude irregular activity" (SIA) described in the literature; we will call its manifestation during sleep "S-SIA." During S-SIA, a small subset of cells becomes active, whereas the rest remain nearly silent, with the same subset of cells active across long sequences of S-SIA episodes. These cells are physiologically indistinguishable from ordinary complex-spike cells; thus, the question arises as to whether they have any special functional correlates. Indeed, many of these cells are found to have place fields encompassing the location where the rat sleeps, raising the possibility that S-SIA is a state of increased alertness in which the animal's location in the environment is represented in the brain.

Mechanisms of Neural Synchrony in the Septohippocampal Pathways Underlying Hippocampal Theta Generation

Using urethane-anesthetized rats, 18 simultaneously recorded septohippocampal cell pairs (36 individual cells), each classified as theta-related according to the criteria of, were studied during four spontaneously occurring hippocampal field conditions: (1) large amplitude irregular activity (LIA) only; (2) the transition from LIA to theta; (3) theta only; and (4) the transition from theta to LIA. The main objective was to study the temporal relationships and degree of neural synchrony between the discharges of the cell pairs, using both time-averaged and time-dependent joint peristimulus time histogram correlation techniques, during the four conditions, to determine their contribution to the control of oscillation and synchrony (theta) in the hippocampus. The study demonstrated that the transition from the LIA state to the theta field state in the hippocampus required a temporal sequence of changes in theta-related cellular activity occurring on average 500 msec preceding the transition: (1) the medial septum inhibits hippocampal theta-OFF cells; (2) medial septal tonic theta-ON cells provide tonic depolarizing inputs to initiate membrane potential oscillations (MPOs) in hippocampal phasic theta-ON cells, whereas medial septal phasic theta-ON cells synchronize the MPOs of hippocampal phasic theta-ON cells and the discharges of hippocampal tonic theta-ON cells. Much of the time preceding the LIA to theta transition is accounted for by recruitment of these theta-related cell populations. Conversely, "turning off" the theta state occurs abruptly and involves the medial septal disinhibition of hippocampal theta-OFF cells.

Hippocampal theta-related cellular activity in the superior colliculus of the urethane-anesthetized rat.

In the present study, 93 cells in the superior colliculus (SC) were recorded extracellularly during the simultaneous occurrence of spontaneous theta field activity, sensory-induced (tail pinch) theta field activity, and large amplitude irregular (LIA) field activity, recorded from an electrode located in the stratum moleculare of the hippocampal formation (HPC). The effect of the intravenous administration of atropine sulfate (ATSO4) was also tested on SC cellular activity. The field activities of theta and LIA were recorded from all layers of the SC and were found to be temporally coherent with the same activities recorded simultaneously from the HPC, during all conditions tested. By using the criteria of Colom and Bland (1987) for the classification of theta-related cells, 75 of 93 cells (81%) were found to be related to the generation of theta field activity in the HPC and 18 of 93 (19%) were nonrelated. All cells recorded discharged in a tonic, nonrhythmic pattern during the theta HPC field states. Of the 75 theta-related cells, 61 (81%) were classified as tonic theta-ON cells and 14 (19%) as tonic theta-OFF cells. Although these cell types were found in all three layers of the SC, the majority of tonic theta-ON cells were recorded in the intermediate layer, and the tonic theta-OFF cells were dispersed evenly between the intermediate layer and the deep layer of the SC. The intravenous administration of ATSO4 abolished theta field activity in the HPC and SC, and the theta-related increase in the discharge rate of all tonic theta-ON cells tested. However, the same treatment did not have any effect on the discharge properties of tonic theta-OFF cells. The same stimuli that resulted in the inhibition of the discharge rates of these cells (tail pinch and electrical stimulation of the PH) in the predrug condition did so after the administration of ATSO4.

Distribution and analysis of hippocampal theta-related cells in the pontine region of the urethane-anesthetized rat.

In the present study 99 cells were recorded in the pontine region of urethane-anesthetized rats during: (1) the spontaneous occurrence of hippocampal formation (HPC) theta field activity; (2) sensory-induced (tail pinch) theta field activity; and (3) large amplitude irregular field activity (LIA). Using the criteria of Colom and Bland (Brain Res 1997;422:277-286) for the classification of theta-related cells, 58/99 cells (59%) were involved with changes in activity related to the occurrence of HPC theta field activity, 24/99 (24%) were non-related, and 17/99 (17%) were related to the sensory input (tail pinch). All cells recorded discharged in a tonic, non-rhythmic pattern in relation to the HPC field activity occurring during the three conditions. Of the 58 theta-related cells, 52 (90%) were classified as tonic theta-ON cells and 6 (10%) as tonic theta-OFF cells. There were no clear regional differences in the distribution of cell types. Statistical analysis of the discharge rates of tonic theta-ON cells during spontaneously occurring theta and tail pinch-induced theta (tested on 48 cells) revealed that 22/48 (46%) of these cells discharged at significantly higher rates during the faster theta field frequencies associated with tail pinches while 26/48 (54%) tonic theta-ON cells did not change discharge rate between the spontaneously occurring theta and the tail pinch-induced theta states. In addition, the discharges of 11/52 (21%) tonic theta-ON cells exhibited weak to moderate correlations with the negative peak of HPC theta field activity recorded from the stratum moleculare of the dentate gyrus. Of the 17 cells related to the sensory stimulation (tail pinch), 12 (71%) cells increased discharge rate during the tail pinch and were classified as sensory activated, while 5 (29%) cells decreased discharge rate during the tail pinch and were classified as sensory inactivated. The results supported the following conclusions: (1) the main cells in the pontine region involved with changes in activity related to the occurrence of HPC theta field activity are tonic theta-ON cells and tonic theta-OFF cells; (2) a subpopulation of tonic theta-ON cells coded the increasing intensity of activation of the ascending brainstem HPC synchronizing pathways by an increase in discharge rate; and (3) a smaller population of cells in the rostral pontine region appeared to be related to sensory stimulation, independent of theta-related activity.

Anatomical, Electrophysiological and Pharmacological Studies of Ascending Brainstem Hippocampal Synchronizing Pathways

BLAND, B. H., S. D. ODDIE. Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways. NEUROSCI BIOBEHAV REV 22(2), 259–273, 1998.—The present review has provided evidence that very potent ascending brainstem hippocampal synchronizing pathways originate in the rostral pons region (RPO and PPT), and ascend to and synapse with several midline caudal diencephalic nuclei (posterior hypothalamic and supramammillary) which send projections to the medial septal region (MS/vDBB). The medial septal region in turn is a critical nodal point, sending projections to limbic structures such as the hippocampal formation, cingulate cortex, and entorhinal cortex. The pontine and diencephalic nuclei appear to play a critical role in determing the translation of increasing levels of activation into moment to moment changes in the frequency of hippocampal theta field and theta-related cellular discharges, relayed to the MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critical role in translating increasing levels of ascending synchronizing activation into moment to moment changes in the amplitude of hippocampal theta field activity and the accompanying rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role through a balance of activity in the septohippocampal cholinergic and GABA-ergic projections. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-ON cells and the GABA-ergic projections act to reduce the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (theta-OFF cells). Both activities must be present for the generation of hippocampal theta and theta-related cellular activities. The balance between the cholinergic and GABA-ergic projections may determine whether hippocampal synchrony (theta) or asynchrony (LIA, large amplitude irregular activity) occurs. These same ascending pathways influence the electrophysiological and pharmacological properties of the neocortex as well. The functional significance of the ascending brainstem synchronizing pathways is the generalized regulation of activities in these cortical structures as they relate to sensorimotor behavior.

Effects of repeated exposures of hydrogen sulphide on rat hippocampal EEG

Exposure to high levels of hydrogen sulphide (H 2S) in humans has been associated with a number of respiratory and neurological symptoms. Acute toxicity following exposure to high concentrations is well-documented, however, there is little scientific information concerning the effects of exposure to low concentrations. The effects of low levels of H 2S on electroencephalographic (EEG) activity in the hippocampus and neocortex were investigated on the freely moving rat (Sprague-Dawley). Hippocampal electrodes were implanted in the dentate gyrus (DG) and CA1 region. Activity was recorded for 10 min just prior to H 2S exposure in the presence of air (pre-exposure). Rats were exposed to H 2S (25, 50, 75 or 100 ppm) for 3 h/day; data was collected during the final 10 min of each exposure. The total power of hippocampal theta activity increased in a concentration-dependent manner in both DG and CA1; repeated exposures for 5 consecutive days resulted in a cumulative effect that required 2 weeks for complete recovery. The effects were found to be highly significant at all concentrations within subjects. Neocortical EEG and LIA (Large Amplitude Irregular Activity) were unaffected. The results demonstrate that repeated exposure to low levels of H 2S can produce cumulative changes in hippocampal function and suggest selectivity of action of this toxicant.

In vivo intracellular recordings of medial septal and diagonal band of Broca neurons: relationships with theta rhythm.

Transmembrane potentials from medial septal and diagonal band of Broca (MS-DBB) neurons and hippocampal field activity were recorded in curarized and urethanized rats. MS-DBB cells were studied during large amplitude irregular activity and during hippocampal theta rhythm, elicited by either sensory (i.e. stroking the fur on the animal's back) or electrical stimulation of the reticularis pontis oralis nucleus (RPO). Three types of cells were described according to their firing pattern and the characteristics of their "intracellular theta" rhythm. Type A neurons displayed continuous rhythmic oscillations in the membrane potential (Vm) of approximately 17 mV. These oscillations generated rhythmic high-frequency spike trains which were phase-locked with hippocampal theta rhythm. Type A cells revealed intracellular theta rhythm even in the absence of hippocampal theta rhythm, suggesting that the activity of this type of cell was the most important in hippocampal theta genesis. Type B cells were characterized by marked postspike after hyperpolarization and intracellular theta oscillations of smaller amplitude than in type A cells. Type C cells revealed a postspike afterdepolarization and a lower amplitude, intracellular theta rhythm only in the presence of hippocampal theta rhythm. Type C neurons could fire slow spikes at depolarizing (46% of cells) or hyperpolarizing (15% of cells) Vms. Type B and C cells were intracellularly stained with Lucifer yellow. Although type B and C neurons revealed dissimilar electrophysiological properties, they had comparable morphological shapes. RPO electrical stimulation generated hippocampal theta rhythm and intracellular theta rhythm in types A and B cells but not in type C cells, and increased the spike rate in type C neurons. Electrical stimulation of the fornix only evoked synaptic responses in type B and C neurons, with antidromic responses being elicited in 12% of type C cells. These results indicate that probably most of the type A rhythmic cells did not receive direct hippocampal feedback and that at least some type C cells were projecting neurons. The present findings demonstrate that theta rhythm oscillations in the Vm of MS-DBB neurons elicit different rhythmic discharge patterns.

Extrinsic modulation of medial septal cell discharges by the ascending brainstem hippocampal synchronizing pathway

Single cells or simultaneously recorded cell pairs in the medial septum (MS) vertical limb of the diagonal band of Broca (vDBB) in the urethane-anesthetized rat were initially classified as either theta-on or non-related according to the system of Colom and Bland (1987, Brain Res 422:277-286). Subgroups of these cells were then studied under various test conditions that included electrical stimulation of the nucleus pontis oralis (PO) or posterior hypothalamus (PH), microinfusion of carbachol into the PO or PH, and the microinfusion of atropine sulfate or procaine hydrochloride into the PH. Electrical stimulation of either the PO or PH induced theta (theta) activity in the hippocampal formation (HPC), and electrical stimulation of the PO resulted in a simultaneous increase in the discharge rate of all MS/vDBB theta-on cells tested, compared to the rates recorded during HPC large-amplitude irregular activity (LIA). Five of the MS/vDBB theta-on cells were tested consecutively with electrical stimulation of the PO and PH, and were shown to be activated in a similar manner in either condition. Microinfusion of carbachol into either the PO or PH resulted in the induction of HPC theta field activity and the simultaneous intense activation of all MS/vDBB theta-on cells tested. Following the microinfusion of either atropine sulfate or procaine into the PH, electrical stimulation of the PO failed to induce HPC theta field activity or the concomitant rhythmic discharges of all MS/vDBB phasic theta-on cells tested. Microinfusing procaine into the PH also abolished the coupling between all MS/vDBB cell pairs during HPC theta field activity including that between two cell pairs that were coupled during HPC LIA. The data support the following conclusions: 1) The brainstem HPC synchronizing pathway originating in the pons region ascends to the medial septum via the midline posterior hypothalamic region; 2) the present results taken together with previous work suggest that a major component of the ascending synchronizing pathway, up to and including the hippocampal formation, is cholinergic, cholinoceptive, or both, and the receptors involved are primarily muscarinic; 3) the midline posterior hypothalamic region is an important source of inputs to the medial septum and their major contribution is to provide frequency-coded inputs to the MS/vDBB for relay into the hippocampal formation.

Extrinsic modulation of theta field activity in the entorhinal cortex of the anesthetized rat

Field recordings of the entorhinal cortex (EC) were studied and compared to those recorded concomitantly in the dentate region of the hippocampal formation (HPC) in the urethane anesthetized rat. The EC, like the HPC, showed two main variations of spontaneous field activity: a desynchronized, large amplitude irregular activity and a synchronized, rhythmic, slow frequency field activity (RSA or theta). Corroborating previous research, a phase reversal was seen across layer II of the EC and when recorded superficial to this layer, EC theta was phase-locked to that recorded from the HPC (dentate). Entorhinal cortex (and HPC) theta could be evoked by the application of moderate tail pinches (sensory stimulation), by pharmacological treatments enhancing cholinergic transmission, and by electrical stimulation of the posterior hypothalamus. Spectral analysis revealed that in all cases, theta was produced coherently across the two limbic structures. Entorhinal cortex (and HPC) production of theta could be abolished by pharmacological treatments disrupting cholinergic transmission, and by reversible procaine inactivation of the medial septal region. Therefore, it was concluded that limbic theta is modulated spontaneously, and with sensory and hypothalamic stimulation through the activity of cells in the medial septal region via muscarinic neurotransmission. It was also hypothesized that the activation of cells in the posterior hypothalamus linearly codes the frequency, and to a lesser extent the power, of EC and HPC theta. Given these findings and the coincidence and coherence of the occurrence of theta across the EC and HPC, it was postulated that it occurs via a parallel mechanism in the two areas.

The Role of the Septohippocampal Pathway in the Regulation of Hippocampal Field Activity and Behavior: Analysis by the Intraseptal Microinfusion of Carbachol, Atropine, and Procaine

The role of the septohippocampal pathway in the regulation of hippocampal field activity and behavior was assessed during the technique of intraseptal microinfusion of carbachol, atropine, and procaine. The effects of these manipulations were assessed by comparing them with the effects of intraseptal saline control infusions on spontaneously occurring motor behavior and their correlated hippocampal field activities. In control conditions hippocampal theta field activity, with up to 40% of the total power concentrated in a 1-Hz band around the peak frequency, was recorded only during type 1 voluntary motor behaviors. Hippocampal large-amplitude irregular activity was recorded during type 2 automatic motor behaviors and during immobility. Microinfusion of carbachol into the MS/vDBB (media septum/vertical limb of the diagonal band of Broca) resulted in continuous theta field activity regardless of what type of motor behavior the animal performed or whether it was immobile. However, under these conditions the performance of a voluntary movement consistently resulted in an upward shift of theta frequency, demonstrating that the frequency of carbachol-elicited type 2 theta can be modulated by the behavioral activation of type 1 theta. The subsequent infusion of atropine abolished the carbachol-elicited theta, while that occurring during type 1 voluntary movement was preserved. In contrast to the selective blockade of carbachol-elicited theta by atropine, procaine suppression of the MS/vDBB abolished both spontaneous movement-related (type 1) theta and carbachol-elicited (type 2) theta. During the postprocaine period theta frequency recovered rapidly in contrast to theta amplitude (power). This result applied to the recovery of both the coactivated type 1 and type 2 theta occurring during spontaneous movement and the carbachol-elicited type 2 theta alone. The behavioral results were discussed within the context of Bland's ( Prog. Neurobiol. 26, 1-54, 1986) sensorimotor model which posits that hippocampal theta activity recorded during voluntary movement represents the coactivation of a cholinergically mediated sensory processing component and a feedback (possibly serotonergic) motor component.

Hippocampal electrical activity in the female rat: the estrous cycle, copulation, parturition, and pup retrieval

Hippocampal electrical activity was examined in female rats across the four phases of the estrous cycle, as well as during copulation, parturition, and pup retrieval. Possible hormonal effects on hippocampal activity were examined by recording daily during struggling and immobility throughout five estrous cycles. No differences in the characteristics of rhythmical slow activity (RSA), large-amplitude irregular activity (LIA), or their relation to behavior were found between the phases of the estrous cycle. Behaviors examined during copulation were lordosis, hopping, and ear wiggling. Lordosis and ear wiggling were both accompanied by irregular waves, with some low frequency RSA also present during lordosis. Hopping was accompanied by RSA which was greater in amplitude and frequency than RSA during walking. Parturition behaviors examined included body extensions, genital or pup licking, and 'body flattening'. Body extensions were found to be associated with irregular hippocampal activity, and appeared to be a Type 2 behavior. Interestingly, sudden suppressions of the hippocampal record lasting 1-5 s often preceded body extensions. Irregular hippocampal activity was present at all times during genital and pup licking. Body flattening was typically accompanied by very high amplitude irregular waves which, although the rats were awake, resembled a sleeping hippocampal pattern. Pup retrieval involved walking and was thus always accompanied by RSA.