Discharge properties of neurons of the median raphe nucleus during hippocampal theta rhythm in the rat

The serotonin (5-HT)-containing median raphe nucleus has been shown to be critically involved in the control of desynchronized (non theta) states of the hippocampal electroencephalogram (EEG). We examined the activity of 181 cells of the median raphe nucleus in the urethane-anesthetized rat and found that approximately 80% (145/181) of them showed changes in activity associated with changes in the hippocampal EEG. These cells were subdivided into theta-on (68%) and theta-off (32%) based on increased or decreased rates of activity with theta, respectively. They were further classified as slow-firing (~1 Hz), moderate-firing (5-11 Hz), or fast-firing (>12 Hz) theta-on or theta-off cells. The slow-firing cells as well as a subset of moderate-firing theta-off cells displayed characteristics of "classic" serotonin-containing raphe neurons. All fast-firing neurons were theta-on cells and showed either tonic or phasic (rhythmical) increases in activity with theta. We propose that: (1) the slow-firing cells (on and off) as well as a subset of moderate-firing theta-off cells are serotonergic neurons; (2) the phasic and tonic fast-firing theta-on cells are GABAergic cells; and (3) these populations of cells mutually interact in the modulation of the hippocampal EEG. An activation of local serotonergic and GABAergic theta-on cells would inhibit 5-HT slow- or moderate-firing theta-off projection cells to release or generate theta, whereas the suppression of serotonergic- or GABAergic theta-on cells would disinhibit 5-HT theta-off cells, resulting in a blockade of theta or a desynchronization of the hippocampal EEG. A role for the median raphe nucleus in memory-associated functions of the hippocampus is discussed.     

Oscillatory entrainment of thalamic neurons by theta rhythm in freely moving rats

The anterior thalamic nuclei are assumed to support episodic memory with anterior thalamic dysfunction a core feature of diencephalic amnesia. To date, the electrophysiological characterization of this region in behaving rodents has been restricted to the anterodorsal nucleus. Here we compared single-unit spikes with population activity in the anteroventral nucleus (AV) of freely moving rats during foraging and during naturally occurring sleep. We identified AV units that synchronize their bursting activity in the 6-11 Hz range. We show for the first time in freely moving rats that a subgroup of AV neurons is strongly entrained by theta oscillations. This feature together with their firing properties and spike shape suggests they be classified as "theta" units. To prove the selectivity of AV theta cells for theta rhythm, we compared the relation of spiking rhythmicity to local field potentials during theta and non-theta periods. The most distinguishable non-theta oscillations in rodent anterior thalamus are sleep spindles. We therefore compared the firing properties of AV units during theta and spindle periods. We found that theta and spindle oscillations differ in their spatial distribution within AV, suggesting separate cellular sources for these oscillations. While theta-bursting neurons were related to the distribution of local field theta power, spindle amplitude was independent of the theta units' position. Slow- and fast-spiking bursting units that are selectively entrained to theta rhythm comprise 23.7% of AV neurons. Our results provide a framework for electrophysiological classification of AV neurons as part of theta limbic circuitry.     

Neural group properties in the rat hippocampus during the theta rhythm

Summary Histochemical staining for a mitochondrial enzyme, cytochrome oxidase demonstrates elongated, rod-like configurations of probable axon terminals in the trigeminal representation of the monkey somatic sensory thalamus. The stained rods are colocalized with similar aggregations of immunocytochemically stained GABAergic thalamic interneurons. Other data suggest the rods also contain clusters of relay neurons projecting to cortical columns, and they are here demonstrated as somatotopic units by micro-electrode mapping and the distribution of afferent fibers. Similar somatotopic rods can be revealed in the rest of the thalamic body representation by the reduction in cytochrome oxidase staining ensuing from the cutting of selected peripheral nerves.     

Serotonin turnover in raphe neurons transplanted into rat hippocampus

Injections of the neurotoxin, 5,7-dihydroxytryptamine, into rostral raphe nuclei in rats reduced serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus to 35-50% of normal levels but only reduced 5-HT synthesis and catabolism by 20-35%. The small reduction in 5-HT metabolism as compared to depletion of 5-HT suggests that 5-HT turnover was increased in nerve terminals that survived the neurotoxin lesion. Transplantation of rat fetal raphe cells into the 5-HT-denervated hippocampus restored 5-HT and 5-HIAA levels and 5-HT synthesis to 125-150% of normal. This demonstrates that transplantation of fetal raphe tissue can restore metabolism to normal levels in the 5-HT denervated hippocampus.     

Activity of reticulospinal neurons during locomotion in the freely behaving lamprey

The reticulospinal (RS) system is the main descending system transmitting commands from the brain to the spinal cord in the lamprey. It is responsible for initiation of locomotion, steering, and equilibrium control. In the present study, we characterize the commands that are sent by the brain to the spinal cord in intact animals via the reticulospinal pathways during locomotion. We have developed a method for recording the activity of larger RS axons in the spinal cord in freely behaving lampreys by means of chronically implanted macroelectrodes. In this paper, the mass activity in the right and left RS pathways is described and the correlations of this activity with different aspects of locomotion are discussed. In quiescent animals, the RS neurons had a low level of activity. A mild activation of RS neurons occurred in response to different sensory stimuli. Unilateral eye illumination evoked activation of the ipsilateral RS neurons. Unilateral illumination of the tail dermal photoreceptors evoked bilateral activation of RS neurons. Water vibration also evoked bilateral activation of RS neurons. Roll tilt evoked activation of the contralateral RS neurons. With longer or more intense sensory stimulation of any modality and laterality, a sharp, massive bilateral activation of the RS system occurred, and the animal started to swim. This high activity of RS neurons and swimming could last for many seconds after termination of the stimulus. There was a positive correlation between the level of activity of RS system and the intensity of locomotion. An asymmetry in the mass activity on the left and right sides occurred during lateral turns with a 30% prevalence (on average) for the ipsilateral side. Rhythmic modulation of the activity in RS pathways, related to the locomotor cycle, often was observed, with its peak coinciding with the electromyographic (EMG) burst in the ipsilateral rostral myotomes. The pattern of vestibular response of RS neurons observed in the quiescent state, that is, activation with contralateral roll tilt, was preserved during locomotion. In addition, an inhibition of their activity with ipsilateral tilt was clearly seen. In the cases when the activity of individual neurons could be traced during swimming, it was found that rhythmic modulation of their firing rate was superimposed on their tonic firing or on their vestibular responses. In conclusion, different aspects of locomotor activity-initiation and termination, vigor of locomotion, steering and equilibrium control-are well reflected in the mass activity of the larger RS neurons.     

Changes in ensemble activity of hippocampus CA1 neurons induced by chronic morphine administration in freely behaving mice

The hippocampus plays an important role in the formation of new memories and spatial navigation. Recently, growing evidence supports the view that it is also involved in addiction to opiates and other drugs. Theoretical and experimental studies suggest that hippocampal neural-network oscillations at specific frequencies and unit firing patterns reflect information of learning and memory encoding. Here, using multichannel recordings from the hippocampal CA1 area in behaving mice, we investigated the phase correlations between the theta (4-10 Hz) and gamma (40-100 Hz) oscillations, and the timing of spikes modulated by these oscillations. Local field potentials and single unit recordings in the CA1 area of mice receiving chronic morphine treatment revealed that the power of the theta rhythm was strongly increased; at the same time, the theta frequency during different behavioral states shifted markedly, and the characteristic coupling of theta and gamma oscillations was altered. Surprisingly, though the gamma oscillation frequency changed, the power of gamma lacking theta did not. Moreover, the timing of pyramidal cell spikes relative to the theta rhythm and the timing of interneuron spikes relative to the gamma rhythm changed during chronic morphine administration. Furthermore, these responses were impaired by a selective D1/D5 receptor antagonist intra-hippocampus injection. These results indicate that chronic morphine administration induced the changes of ensemble activity in the CA1 area, and these changes were dependent on local dopamine receptor activation.     

Rostral ventrolateral medullary and caudal medullary raphe neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

1. The current study is the first to identify medullary neurons whose naturally occurring discharges were correlated to the 10-Hz rhythm in sympathetic nerve discharge (SND). Spike-triggered averaging showed that 44 of 164 rostral ventrolateral medullary (RVLM) and 44 of 174 caudal medullary raphe neurons had activity correlated to the 10-Hz rhythm in inferior cardiac postganglionic SND of 23 baroreceptor-denervated, decerebrate cats. 2. When the frequency of the rhythm in SND was decreased by lowering body temperature, the discharges of the 10 neurons tested (6 RVLM and 4 raphe) remained locked to the peak of the next 10-Hz sympathetic nerve slow wave rather than to the peak of the preceding slow wave. This observation supports the contention that the 10-Hz rhythm in basal SND was generated in the brain stem rather than in the spinal cord. 3. Frequency-domain analysis was used to characterize further the relationship between the 10-Hz rhythm in SND and the discharges of 30 RVLM and 24 raphe neurons. The autospectra of the discharges of eight RVLM and four raphe neurons contained a sharp peak near 10 Hz, although the mean firing rates of these neurons were lower than the frequency of the rhythm in SND. Coherence values as high as 0.76 characterized the relationship between the discharges of these "rhythmically firing neurons" and the 10-Hz rhythm in SND. A coherence value of 1.0 indicates a perfect correlation. The autospectra of the discharges of the 22 RVLM and 20 raphe neurons did not contain a peak near 10 Hz. The mean firing rates and coherence values relating the discharges of these "nonrhythmically firing neurons" and the 10-Hz rhythm in SND were significantly lower than those for the rhythmically firing neurons. Because the frequency of the population rhythm recorded from the inferior cardiac nerve was higher than the firing rates of individual medullary neurons, the 10-Hz rhythm in SND appears to be an emergent property of a network of neurons whose discharges are probabilistically related to the population rhythm. 4. In addition to the peak near 10-Hz, the autospectrum of SND often contained considerable power at frequencies < 6 Hz. This component of SND is called the 2- to 6-Hz rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dibutyryl cyclic AMP has epileptogenic potential in the hippocampus of freely behaving rats: a combined EEG-intracerebral microdialysis study.

The effects of dibutyryl cyclic AMP were studied with the combined EEG-intracerebral microdialysis technique in the hippocampus of freely behaving rats. It was found that intrahippocampal microdialysis with this drug produced epileptiform EEG events associated with limbic type behavioral seizures. The dibutyryl cyclic AMP-induced seizures developed with a long latency, and persisted for a prolonged period even after the removal of the drug from the microdialysis fluid. Similar EEG or behavioral manifestations did not occur during intrahippocampal microdialysis with artificial cerebrospinal fluid or ATP solutions. These data suggest that in the hippocampus, in vivo, the cyclic AMP second messenger system may be involved in potentially epileptogenic excitatory processes.     

Firing of inferior colliculus auditory neurons is phase-locked to the hippocampus theta rhythm during paradoxical sleep and waking

The activity of 52 single auditory units in the central nucleus of the inferior colliculus (IC) was recorded along with cortical and hippocampal (CA1) electrograms and neck muscle electromyograms in behaving, head-restrained guinea pigs during paradoxical sleep (PS) and wakefulness. Sixteen (30%) of the IC auditory units showed positive correlation with the hippocampal theta () rhythm: 8 (15%) were rhythmic with phase-locking (type 1), 8 (15%) showed only phase-locking with no rhythmicity (type 2), while 70% did not show any correlation to hippocampal rhythm (type 3). During wakefulness IC neurons (4 of 13) showed a higher synchrony with hippocampal when sound-stimulated at the unit's characteristic frequency. During PS all IC auditory neurons recorded presented some hippocampal correlation: 40% were rhythmic and phase-locked to the frequency and 60% were nonrhythmic maintaining the phase-locking. Shifts in the angle of phase-locking to the rhythm were observed during PS. It is suggested that the hippocampal rhythm may play the part of an internal clock, adding a temporal dimension to the processing of auditory sensory information.     

Size of CA1-evoked synaptic potentials is related to theta rhythm phase in rat hippocampus

Cholinergic and GABAergic neurons projecting to the hippocampus fire with specific phase relations to theta rhythm oscillations in the electroencephalogram (EEG). To determine if this phasic input has an impact on synaptic transmission within the hippocampus, we recorded evoked population excitatory postsynaptic potential (EPSPs) during different phases of theta rhythm by using techniques similar to those described in Rudell and Fox. Synaptic potentials elicited by stimulation of region CA3 of the contralateral hippocampus were recorded in region CA1 and CA3. In these experiments, the initial slope of evoked potentials showed a change in magnitude during different phases of the theta rhythm recorded in the dentate fissure, with individual trials showing an average of 9.5% change in slope of potentials, and the average across all experiments showing a change of 7.8%. Evoked potentials were maximal 18 degrees after the positive peak of the dentate fissure theta EEG. These potentials were also smaller by 18.2% during theta as opposed to non-theta states. Phasic changes in modulation of synaptic transmission could contribute to phase precession of hippocampal place cells and could enhance storage of new sequences of activity as demonstrated by computational models.     

Technique for stabilizing the presentation of auditory stimuli in the freely behaving rat

A miniature speaker system which is rigidly mounted in the external auditory meatus has been developed to solve the problem of presenting a constant auditory stimulus to freely behaving rats. Intensity across frequencies is maintained at constant levels with an easily constructed programmable attenuator.     

Continuous perfusion under pressure using several tubes in the freely behaving rat

The technique described allows connecting several tubes and electric wires to a rat, leaving the latter free to move. The principle of the technique is the twisting of the tubes and electric wires together to form a helix. This converts torsional stresses on tubes and wires into longitudinal stresses.     

Synaptic plasticity in the hippocampus during afferent activation reproducing the pattern of the theta rhythm (theta plasticity)

This review summarizes data on the plasticity of hippocampal synaptic pathways in conditions of afferent activation modeling the electrical activity of neurons during the theta rhythm. Activation with short trains of stimuli with frequencies of about 5 Hz efficiently induces long-term potentiation, i.e., stable facilitation of synaptic transmission. Contrarily, single stimuli presented at the same frequency “depotentiate” synapses or even induce long-term depression. Combined theta activity at two synaptic inputs, in phase with each other, induces long-term potentiation, while combined activity in antiphase produces long-term depression of the weakly-activated input (associative long-term potentiation and depression). Short trains of single stimuli at a frequency of 5 Hz induce heterosynaptic short-term depression: the efficiency of all synaptic inputs is decreased for time periods of the order of 1 min. Apart from changes in synaptic efficiency, theta activation affects the ability to induce synaptic rearrangements in conditions of subsequent afferent activation (“cryptic” plasticity). Thus, virtually all known types of synaptic plasticity are efficiently induced by afferent activation of the pattern of the hippocampal theta rhythm, which suggests the possible mechanisms for its roles in learning and memory processes. Translated from Zhurnal Vysshei Nerynoi Deyatel'nosti, Vol. 48, No. 1, pp. 3–18, January–February, 1998.     

Neural signature of taste familiarity in the gustatory cortex of the freely behaving rat

Ample data indicate that the gustatory cortex (GC) subserves the processing, encoding, and storage of taste information. To further elucidate the neural processes involved, we recorded multi-unit activity in the GC of the freely behaving rat as it became familiar with a novel tastant. Exposure to the tastant was performed over three 40- to 50-min sessions, 24 h apart. In each session, the tastant was presented repeatedly, 1 s at a time, with 10- to 12-s inter-trial intervals. The neural response to the tastant typically lasted 7 s. Our results show that the average neuronal response to the tastant increased as this tastant became familiar, but this increase was detected only during the last 5 s of the response. The increased response was not generalized to another tastant. Furthermore, our analysis suggests that specific neuronal populations subserve the processing of familiarity of specific tastants. The signature of familiarity was not detected in the course of the familiarization session, but only on the subsequent day, suggesting that its development involves slow post-acquisition processes. Our data are in line with the notion that GC neurons process multiple taste attributes, familiarity included, during different temporal phases of their response. The data also suggest that by default the brain considers a taste stimulus as novel, unless proven otherwise.     

Regulation of IPSP theta rhythm by muscarinic receptors and endocannabinoids in hippocampus

Theta rhythms are behaviorally relevant electrical oscillations in the mammalian brain, particularly the hippocampus. In many cases, theta oscillations are shaped by inhibitory postsynaptic potentials (IPSPs) that are driven by glutamatergic and/or cholinergic inputs. Here we show that hippocampal theta rhythm IPSPs induced in the CA1 region by muscarinic acetylcholine receptors independent of all glutamate receptors can be briefly interrupted by action potential-induced, retrograde endocannabinoid release. Theta IPSPs can be recorded in CA1 pyramidal cell somata surgically isolated from CA3, subiculum, and even from their own apical dendrites. These results suggest that perisomatic-targeting interneurons whose output is subject to inhibition by endocannabinoids are the likely source of theta IPSPs. Interneurons having these properties include the cholecystokinin-containing cells. Simultaneous recordings from pyramidal cell pairs reveal synchronous theta-frequency IPSPs in neighboring pyramidal cells, suggesting that these IPSPs may help entrain or modulate small groups of pyramidal cells.     

Effect of posterior hypothalamic injection of procaine on the hippocampal theta rhythm in freely moving cats

Earlier in vivo studies conducted on freely moving and anesthetized rats demonstrated that the posterior hypothalamus (PH) comprises pathways critical for producing the synchronous hippocampal formation (HPC) theta rhythm. In addition, these findings suggested that the frequency of the HPC theta was encoded in the PH and then was fed via the medial forebrain bundle to the medial septum and HPC. In the present study we attempted to verify this hypothesis with use of a different in vivo model--freely moving cats. The microinjection of the local anaesthetic, procaine, into the PH region reversibly suppressed the spontaneous as well as sensory and electrically induced HPC theta. However, in contrast to rats, in freely moving cats microinjection of procaine into the PH reduced the amplitude of the HPC theta but had no effect on theta frequency. We conclude that in freely moving cats the PH region comprises a critical part of the ascending brainstem pathway, for production of the HPC theta rhythm. In contrast to rats, in freely moving cats ascending inputs from the brainstem to the PH contribute mainly to the amplitude of the HPC theta rhythm.     

Neuronal correlates of siphon withdrawal in freely behaving Aplysia.

1. Central neuronal mechanisms of siphon withdrawal in Aplysia were studied for the first time in intact, freely behaving animals by means of population recordings from implanted whole-nerve cuff electrodes. Intracellular follow-up studies were then conducted when the same animal was reduced to a semi-intact preparation. 2. Background spontaneous activity in the siphon nerve consisted of low-frequency firing of a population of efferent units containing identified siphon motoneurons. 3. Spontaneous patterned bursts of efferent activity occurred irregularly and were associated with all-or-nothing contractions of the parapodia, gill, and siphon. Spontaneous bursts were due to centrally generated activity in the interneuron II (INT II) network, an oscillatory network with endogenous pacemaker properties. 4. In intact animals, even weak tactile stimuli to the siphon typically triggered an INTII burst shortly after the stimulus-locked efferent activity. Thus, the stimulus can phase-advance the INT II oscillator. In semi-intact preparations, short-latency INT II bursts were triggered less less frequently and required more intense stimuli. 5. With weak to moderate-intensity stimuli in intact animals, the presence of short-latency triggered INT II bursts largely determined the duration of the siphon component and amplitude of the gill component of the withdrawal reflex. 6. When stimuli were repeated over a range of interstimulus intervals (from 60 to 1 min), the likelihood of triggering a short-latency INT II burst die not change systematically. Thus, the ability of the siphon stimulus to stably entrain the all-or-none INT II component over a wide range of intervals will interact behaviorally with the decrement of the monosynaptic component of the reflex with repetition.     

Model of gradual phase shift of theta rhythm in the rat

CA1 pyramidal cell is modeled by a linked series of passive compartments representing the soma and different parts of the dendritic tree. Intracellular postsynaptic potentials are simulated by conductance changes at one or more compartments. By assuming an infinite homogeneous extracellular medium and a particular geometrical arrangement of pyramidal cells, field potential profiles are generated from the current source-sinks of the compartments. The pyramidal cells are driven at the theta (theta)-frequency at different sites of the dendritic tree in order to simulate external driving of hippocampus by the septal cells. Inhibitory or excitatory driving at different sites gives extracellular dipole fields of different null zones and maxima. Phase reversal (180 degrees) of a dipole field generated by synchronous synaptic currents is completed within a depth of 150 micron. By driving two spatially distinct but overlapping dipole fields slightly phase-shifted (30-90 degrees) from each other, the resultant field shows a gradual phase shift of 180 degrees in over 400 micron depth and no (stationary) null zones. The latter field correspond to the theta-profiles seen in the freely moving rat. Somatic inhibition is proposed to be the synaptic process generating the theta-field potentials (named dipole I) in the urethananesthetized or curarized rat. Dipole I has amplitude maxima at the basal dendritic and the distal apical dendritic layers, with a distinct null zone and phase reversal at the apical side of the CA1 pyramidal cell layer. Rhythmic distal dendritic excitation, time-delayed to somatic inhibition, is proposed to be the additional dipole (dipole II) found in freely moving rats. The combination of dipoles I and II, phase-shifted from each other, causes the gradual theta-field phase shift. Experimental studies indicate that dipole I is atropine-sensitive and probably driven by a cholinergic septohippocampal input, whereas dipole II is atropine-resistant and may come from a pathway through both the septum and the entorhinal cortex. Variations of the phase profiles of the theta-field in freely moving rats by administration of anesthetic and cholinergic drugs and by normal changes in theta-frequency could be accounted for by the proposed model. Changes of the intracellular membrane potential, cellular firing rate, and evoked excitability at different phases of the theta-rhythm in anesthetized and freely moving rats can be predicted from the model, and they are in general agreement with the extant literature. In conclusion, theta-field is generated by a rhythmic somatic inhibition phase-shifted with a distal apical-dendritic excitation.(ABSTRACT TRUNCATED AT 400 WORDS)