Posterior hypothalamic nucleus deep brain stimulation restores locomotion in rats with haloperidol-induced akinesia but not skilled forelimb use in pellet reaching and lever pressing.

Recent studies have shown that electrical stimulation of the posterior hypothalamic nucleus (PH) facilitates locomotion in control rats, and rats were made akinetic by dopaminergic blockade via haloperidol or dopamine depletion by the neurotoxin 6-hydroxydopamine. These findings suggest that PH stimulation might be a promising treatment for akinesia associated with dopamine loss in Parkinson's disease. The present study further examined the positive effects of PH stimulation on behavior by characterizing its potential facilitatory effects on tasks that require skilled movements. Rats were trained to reach for food pellets with a forelimb (skilled reaching) or press a bar in an operant conditioning task for food. PH stimulation in undrugged rats not only facilitated locomotion in each of the tasks, but also impaired performance of the skilled movement components of the tasks. Haloperidol reduced locomotion and skilled movement, and PH stimulation only restored locomotion. The results are discussed in relation to the idea that PH stimulation selectively facilitates locomotor behavior and may have limited use in restoring impairments in skilled movements and consummatory behavior that results from dopaminergic depletion.

Deep brain stimulation of the posterior hypothalamic nucleus reverses akinesia in bilaterally 6-hydroxydopamine-lesioned rats.

Deep brain stimulation (DBS) of the basal ganglia motor circuitry is a highly effective treatment for the debilitating motor symptoms of Parkinson's disease (PD). However, recent findings have indicated promising potential for PD therapy with DBS in brain structures outside the basal ganglia. For example, high frequency stimulation of the posterior hypothalamic nucleus (PH) can reverse haloperidol-induced akinesia in rats [Jackson J, Young CK, Hu B, Bland BH (2008) High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal-striatal theta coherence following haloperidol-induced catalepsy. Exp Neurol 213:210-219]. In the current study, we used the bilateral 6-hydroxydopamine lesion model of Parkinsonian akinesia in male Long-Evans rats to further explore the efficacy of PH DBS. The application of PH DBS in lesioned animals reversed akinesia in an active avoidance paradigm with increased latency compared to pre-lesion performance. The dramatic reversal of akinesia in two models of rodent Parkinsonism by PH DBS warrants further exploration of its therapeutic potential.

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 6s. 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.

Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration.

The current review advances the argument that it is naïve to ascribe a unitary function to the hippocampal formation (HPC). Rather, it is more productive to consider the hippocampal formation as consisting of a number of subsystems, each subsystem defined by its own particular neural circuitry. Among examples of neural circuitry appearing in current hippocampal literature are theta, beta and gamma oscillations, sharp waves, place cells and head orientation cells. Data are reviewed supporting the case that theta band oscillation and synchrony is involved in mechanisms underlying sensorimotor integration. Specifically, the neural circuitry underlying the production of oscillation and synchrony (theta) in limbic cortex and associated structures function in the capacity of providing voluntary motor systems with continually updated feedback on their performance relative to changing environmental (sensory) conditions. A crucial aspect of this performance is the intensity with which the motor programs are initiated and maintained. The ascending brainstem HPC synchronizing pathways make the primary contribution in this regard. These pathways originate in the rostral pontine region, ascend and synapse with caudal diencephalic nuclei, which in turn send projections to the medial septal region. The medial septum functions as the node in the ascending pathways, sending both cholinergic and GABA-ergic projections to the HPC. An updated version of the sensorimotor integration model including anatomical details is presented and discussed.

[Basic micro-electrophysiologic techniques used in neurobiology]. / Podstawowe techniki mikroelektrofizjologiczne w neurobiologii.

Problems of application of microelectrophysiological techniques in neurobiology are addressed. Authors focused on five basic recording techniques: micro-EEG, multi unit activity, single unit activity, intracellular recording and patch clamp techniques.

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.

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 formation theta activity and movement selection.

Hippocampal theta activity results from activation in the ascending synchronizing system. It occurs during sensory/signal processing prior to and coincident with voluntary movements in mammals. The experiments summarized here suggest that it is involved in the organization of motor behaviour. (1) Procaine (a local anaesthetic) infused into the medial septum (MS) abolishes hippocampal theta activity and running behaviour elicited by electrical posterior hypothalamic (PH) stimulation. This indicates that movement elicited by PH stimulation, is dependent on ascending hypothalamo-septal circuitry. (2) Theta can also be recorded in immobile rats prior to the initiation of lateral dodging movements they make in response to conspecific rats attempting to steal their food. Following infusion of atropine into the MS, theta recorded during immobility is abolished and the rats are severely impaired at initiating movements in defence of their food. It is suggested that atropine-sensitive theta is involved in the initiation of movements made by rats in response to sensory stimuli. (3) Rats with fimbria-fornix transections were also less likely to engage in lateral dodging movements in defence of their food, were hyperactive, less thigmotaxic, and defecated more often, compared to control animals. Depth profile analysis of hippocampal field activity in lesioned animals revealed an absence of theta during electrical or chemical pons stimulation. These findings provide evidence that these neural systems are involved in signal processing relevant to movements underlying adaptive behaviour.

Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways.

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 determining 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.

Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording.

Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement.

Evidence for differential control of posterior hypothalamic, supramammillary, and medial mammillary theta-related cellular discharge by ascending and descending pathways.

Single-unit discharge was recorded from cells in the posterior hypothalamic nucleus (PH), supramammillary nucleus (SuM), and medial mammillary nucleus (MM) during hippocampal theta (theta) elicited by stimulation of the reticular nucleus pontis oralis (RPO). In agreement with previously published work, theta-related cells in the PH (12 cells) were all classified as tonic theta-ON (increased tonic discharge rate during hippocampal theta), whereas those in the SuM (9 cells) and MM (15 cells) were all classified as phasic theta-ON (rhythmic discharge, in phase with ongoing theta). The effect of RPO stimulation on cell discharge was tested after hippocampal theta was abolished by infusion of procaine into the medial septum/vertical limb of the diagonal band. The RPO-elicited discharge patterns of all PH tonic theta-ON cells and all SuM phasic theta-ON cells survived septal procaine infusion. Further, the discharge rate of PH cells and the frequency of burst discharge of SuM cells during RPO stimulation both increased after the infusion. In contrast, septal procaine infusion abolished the RPO-elicited rhythmic discharge pattern in MM phasic theta-ON cells and attenuated their discharge rates. These results indicate that the PH and SuM form parts of an ascending system mediating hippocampal theta, whereas the MM receives (and perhaps relays to other parts of the limbic system) rhythmic input descending from the septo-hippocampal system. In addition, PH and SuM receive descending inputs that limit the discharge rates of their theta-related cells during hippocampal theta.

Thiopental uncouples hippocampal and cortical synchronized electroencephalographic activity.

BACKGROUND: Thiopental produces a concentration-dependent continuum of effects on the cortical electroencephalogram (EEG) that has been linked to behavioral measures of anesthetic depth. The complexity of the response, however, limits a clear insight into the neurophysiologic actions of thiopental. The current study investigated thiopental actions on cortical EEG and hippocampal electrical activity, to determine whether similar effects occur on both structures and to compare synchronized activity between these structures. METHODS: Thiopental was administered intravenously via an implanted catheter in freely moving rats. Arterial blood oxygen/carbon dioxide concentration, thiopental concentrations, and temperature were monitored and controlled. Neocortical EEG was recorded from implanted dural surface electrodes and hippocampal neuron electrical activity was recorded from stereotaxically placed microelectrodes. Pharmacokinetic models were used to determine effect site concentrations. RESULTS: Thiopental produced an increase in EEG frequency and amplitude at low concentrations (15-20 micrograms/ml total plasma, approximately 10 microM unbound), which produced a loss of righting reflex. This was followed by a frequency decrease and burst suppression activity at higher concentrations (50-80 micrograms/ml, approximately 60 microM), which produced a loss of tail pinch and corneal reflexes. Higher concentrations of thiopental ( > 60 micrograms/ml) uncoupled synchronized burst discharges recorded in hippocampus and cortex. Isoelectric EEG activity was associated with concentrations of 70-90 micrograms/ml (approximately 80 microM) and a deep level of anesthesia; motor reflexes were abolished, although cardiovascular reflexes remained. In all frequency bands, similar concentration-EEG effect relationships were observed for cortical and hippocampal signals, only differing in the magnitude of response. A reversed progression of effects was observed on recovery. CONCLUSIONS: The results confirm earlier findings in humans and animals and demonstrate that both the hippocampus and neocortex exhibit burst suppression and isoelectric activity during thiopental anesthesia. Thiopental-induced synchronized burst activity was depressed by progressively higher concentrations. The lost synchronization suggests a depression of synaptic coupling between cortical structures contributes to anesthesia.

Intraseptal microinfusion of muscimol: effects on hippocampal formation theta field activity and phasic theta-ON cell discharges.

The effect of intraseptal microinfusions of the GABA-A agonist muscimol on spontaneously occurring or hypothalamically induced hippocampal formation (HPC) theta field activity and the simultaneously occurring discharge properties of CA1 pyramidal and dentate granule layer phasic theta-ON cells, was investigated in urethane-anesthetized rats. The microinfusion of 5.0-12.5 nmol of muscimol into the medical septum/vertical limb of the diagonal band of Broca (MS/vDBB) resulted in a progressive reduction (beginning 5 min postinfusion) in the power (amplitude) and finally the total loss of theta field activity. In contrast, theta field frequency remained unaffected during the entire postinfusion period that theta field activity was present. In the time immediately following the first 1-min intraseptal microinfusion of 5 nmol muscimol, (before changes in theta amplitude occurred) a brief period of increased phasic theta-ON cell excitability was noted. This was manifested as an increase in the number of discharges per rhythmic burst. Associated with the progressive reduction of the amplitude of theta field activity, phasic theta-ON cell discharge rates progressively decreased for a period beginning 5 min postinfusion of 5 nmol muscimol. Despite the progressive decrease in the number of discharges and a noticeable reduction in the degree of rhythmicity, phasic theta-ON cells maintained their preferred timing of discharges in relation to the phase of theta field activity, while the latter was present. Just prior to the complete abolishment of theta field activity, phasic theta-ON cells ceased discharging. During the period when theta field activity was replaced on low amplitude asynchronous activity, phasic theta-ON cells discharged in bursts correlated with every occurrence of sharp wave field activity. The results support the following conclusions: (1) the brief excitatory effect on HPC theta-ON cell discharges may be correlated pharmacologically with an initial brief increase in HPC ACh turnover. The reduction of phasic theta-ON cell discharges and theta field activity may be correlated with the longer lasting reduction of HPC ACh turnover, controlled by MS/vDBB GABA-A inputs to MS/vDBB cholinergic septohippocampal neurons, possibly along with a direct inhibition of the GABAergic septohippocampal projection; (2) the primary contribution of the MS/vDBB nuclei, as a nodal point in the ascending brainstem HPC synchronizing system, is the modulation of the amplitude of HPC formation theta field activity and secondarily to relay frequency-coded inputs from the posterior hypothalamic region (posterior and supramammillary nuclei); (3) HPC theta and sharp wave field activity represent functionally distinct neural inputs to the same population of phasic theta-ON cells located in both the CA1 pyramidal and dentate granule cell layers.

Intraseptal procaine abolishes hypothalamic stimulation-induced wheel-running and hippocampal theta field activity in rats.

Rats were implanted chronically with hippocampal recording electrodes, a microinfusion guide cannula aimed at the medial septal nucleus, and an electrode for electrical stimulation of the posterior hypothalamic nucleus (PH). PH stimulation elicited running in rats placed in a wheel and simultaneously occurring hippocampal theta field activity (HPC-theta). In the preprocaine (PRE) testing condition, a positive linear relationship was demonstrated among the intensity of electrical stimulation of the PH, wheel-running speed, and the peak frequency of HPC-theta. HPC-theta amplitude reached an asymptote at the lowest levels of electrical stimulation of the PH. Procaine hydrochloride (1.5 microliters, 20% solution), a local anesthetic, was then infused into the medial septal nucleus (MS). Five minutes after the infusion, PH stimulation no longer induced wheel-running behavior or HPC-theta, and the remaining irregular field activity was significantly reduced in amplitude. Fifteen minutes after the procaine infusion, PH stimulation still did not elicit HPC-theta or running behavior in the majority of animals but did evoke large-amplitude sharp-waves. Thirty minutes after the procaine infusion, PH stimulation again elicited HPC-theta and running behavior, but HPC-theta peak frequency and running speeds were both significantly reduced compared with PRE values. Forty-five minutes after the infusion, HPC-theta amplitude had recovered to PRE values, but HPC-theta frequency and running speeds elicited by PH stimulation were still significantly reduced. By 60 min after procaine administration, the amplitude and frequency of HPC-theta and the running speeds elicited by PH stimulation recovered to PRE values. Multiple regression analysis revealed that the recovery pattern of running behavior reflected the frequency rather than the amplitude of HPC-theta. Neither saline control infusions into the MS nor procaine infusions into the lateral septum and paraventricular thalamic nucleus affected HPC-theta or running behavior. These findings are consistent with the notion that both the locomotor activity and "movement-related" HPC-theta frequency induced by electrically stimulating the PH were attributable to ascending activation of a hypothalamo-septal pathway and not to activation of descending brainstem or peripheral motor systems.

Ascending projections of the posterior nucleus of the hypothalamus: PHA-L analysis in the rat.

With the exception of a report by R.B. Veazey, D.G. Amaral, and W.M. Cowan (1982, J. Comp. Neurol. 207:135-156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of stria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices. The diversity of PH projections to subcortical and cortical "limbic-related" sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events.

Discharge patterns of hippocampal theta-related cells in the caudal diencephalon of the urethan-anesthetized rat.

1. Single-unit discharge patterns of cells in specific nuclei of the caudal diencephalon were characterized in relation to simultaneously recorded field activity from the stratum moleculare of the dentate gyrus according to the criteria that have been used previously to classify cells in the hippocampal formation (including entorhinal cortex), medial septum, and cingulate cortex. Theta (theta)-related cells were classified as 1) tonic theta-ON, if they discharged nonrhythmically and increased their discharge rates during hippocampal theta relative to large, irregular hippocampal field activity (LIA); 2) tonic theta-OFF, if they discharged nonrhythmically and decreased their discharge rates during theta relative to LIA; or 3) phasic theta-ON, if they discharged rhythmically and in phase with ongoing theta, but nonrhythmically during LIA. Cells not meeting any of the above criteria were classified as nonrelated. 2. Recordings were obtained in a total of 127 cells from the caudal diencephalon. Recordings were made in 54 cells from the posterior hypothalamic nucleus (PH), 16 from the supramammillary nucleus (SuM), 20 from the PH/SuM border, and 23 from the medial mammillary nucleus (MM). Recordings were also made from nine cells from the central medial nucleus of the thalamus (CM) and five from the dorsomedial hypothalamic nucleus (DMH). 3. Of the 54 PH cells, 43 (80%) were classified as tonic theta-ON and 11 (20%) as nonrelated. Tonic theta-ON cells in the PH discharged at significantly higher rates during theta, either occurring spontaneously (9.6 +/- 1.7 Hz, mean +/- SE) or elicited with a tail pinch (TP theta; 10.6 +/- 1.9 Hz), than during LIA (3.6 +/- 1.4 Hz). Of the nine CM cells, seven (78%) were tonic theta-ON and two (22%) were nonrelated. Tonic theta-ON cells discharged at significantly higher rates during theta (17.5 +/- 7.8 Hz) or TP theta (18.0 +/- 7.1 Hz) than during LIA (7.3 +/- 4.8 Hz). All DMH cells were nonrelated. 4. Of the 20 PH/SuM border cells, 15 (75%) were classified as tonic theta-OFF and discharged at significantly higher rates during LIA (5.3 +/- 1.5 Hz) than during theta (0.8 +/- 0.4 Hz) or TP theta (0.4 +/- 0.3 Hz). Five (25%) cells in the PH/SuM border were nonrelated. 5. All of the 16 cells (100%) recorded from the body of the SuM were phasic theta-ON. The discharge rates of these cells did not change significantly across hippocampal field states (LIA = 8.3 +/- 1.6; theta = 7.3 +/- 1.6; TP theta = 8.6 +/- 1.7 Hz).(ABSTRACT TRUNCATED AT 400 WORDS)

Classification of theta-related cells in the entorhinal cortex: cell discharges are controlled by the ascending brainstem synchronizing pathway in parallel with hippocampal theta-related cells.

Single-unit discharge patterns of entorhinal cortex (EC) cells were characterized in relation to simultaneously recorded hippocampal (HPC) field activity according to criteria used previously to classify cells in the hippocampal formation, medial septum, cingulate cortex, and caudal diencephalon. EC cells related to HPC theta field activity were classified as 1) phasic theta-on, if they discharged rhythmically, and in phase, with ongoing HPC theta, but nonrhythmically during large, irregular hippocampal field activity (LIA); 2) tonic theta-on, if they discharged nonrhythmically and increased their discharge rates during HPC theta relative to LIA; 3) phasic theta-off, if they discharged rhythmically, and in phase, with ongoing HPC theta, but increased their discharge rates during LIA; and 4) tonic theta-off, if they discharged nonrhythmically and decreased their discharge rates during HPC theta relative to LIA. Cells not meeting any of these criteria were classified as nonrelated. A total of 168 EC cells were recorded, and of these 56 (33%) were classified as theta related, with the remaining 112 (67%) classified as nonrelated. Of the 56 theta-related cells, 41 (73%) had significantly higher discharge rates during HPC theta than during LIA and were classified as theta-on cells (15 phasic theta-on cells and 26 tonic theta-on cells). Nine of the 26 tonic theta-on cells showed a phase relation of their arrhythmic discharges to simultaneously recorded HPC theta field activity. EC phasic theta-on cells did not discharge preferentially on any portion of the HPC theta field recorded from the region of the stratum moleculare of the dentate gyrus. In general, cells classified as phasic revealed a wide distribution of phase preferences. The remaining 15 (26.7%) cells were classified as theta-off cells and discharged at higher rates during HPC LIA than during HPC theta field activity (3 phasic theta-off cells and 12 tonic theta-off cells). Systemic administration of physostigmine significantly increased the discharge rate of tonic and phasic theta-on cells relative to LIA. Electrical stimulation in the posterior hypothalamic region (PH) significantly increased the discharge rate of EC theta-on cells and significantly decreased the discharge rate of EC theta-off cells relative to HPC LIA. The discharge rates of nonrelated EC cells were not influenced by electrical stimulation of the PH. Procaine microinfusion into the medical septum (MS) abolished spontaneously occurring HPC theta and theta induced with PH stimulation. In addition, 5 min after MS procaine, the ability of PH stimulation to modulate EC theta-on cell discharge was abolished. The modulation of cellular discharges produced by PH stimulation recovered by 60 min post-procaine infusion into the MS. The findings support two main conclusions: 1) theta-related cells in the EC are comprised of two main populations of cells, theta-on and theta-off, similar to other regions of limbic cortex and nuclei of the ascending brainstem synchronizing pathway; 2) the ascending brainstem synchronizing pathway exerts both similar and parallel effects on theta-related cells in entorhinal cortex and hippocampus.

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.

The midline posterior hypothalamic region comprises a critical part of the ascending brainstem hippocampal synchronizing pathway.

Electrical stimulation and microinfusion techniques were utilized in acute experiments on urethane-anesthetized rats in order to evaluate the hypothesis that the posterior hypothalamic and supramammillary nuclei comprise a critical part of the ascending brainstem pathway for producing synchronous hippocampal formation (HPC) field activity (theta). Given confirmation of this hypothesis a second objective was to determine the nature of the contribution made by this midline posterior hypothalamic region (PH) to the frequency and amplitude components of HPC theta field activity. The cholinergic nature of the ascending pathway was also examined. Reversible inactivation of the PH was achieved by microinfusion of the local anesthetic procaine hydrochloride. The efficacy of and recovery from procaine inactivation of the PH was quantitatively analyzed either by electrical stimulation of the nucleus pontis oralis (PO) (two experiments) or the PH (four experiments). The results are summarized under the following three headings: 1) The first is the effect of procaine inactivation of the PH on HPC theta elicited caudal to, at the level of, or rostral to the PH. All HPC theta induced caudal to the PH (spontaneous theta, tail pinch-induced theta, and theta produced by electrical stimulation of the PO) was totally abolished for a minimum 10-min period. HPC theta induced rostral to the PH by the intrahippocampal infusion of carbachol was unaffected, while HPC theta induced by infusions of carbachol into either the medial septum (MS) or PH was reduced in amplitude with no effect on frequency. 2) Next are comparisons of pre- and post-PH procaine trials of electrical stimulation of the PO and PH. In all experiments, regardless of the anatomical locus or technique used to induce HPC theta, pre- and post-PH procaine comparisons of the PO and PH stimulation trials revealed that frequency modulation of HPC theta recovered significantly more slowly than amplitude. 3) Last is the effect of electrical stimulation of the PO and PH on HPC theta induced by carbachol infusions at the level of the HPC, MS, or PH. In all experiments, electrical stimulation of both the PO and PH, at appropriate intensities, resulted in increasing HPC theta frequencies above the frequency induced by the infusion of carbachol into the HPC, MS, and PH. In addition, the post-carbachol HPC theta frequencies induced by electrical stimulation were significantly higher than those produced in the pre-carbachol conditions.(ABSTRACT TRUNCATED AT 400 WORDS)