Changes In Multiple Unit Activity Research Articles

Lesions of the thalamic reticular nucleus or the basal forebrain impair Pavlovian eyeblink conditioning and attenuate learning-related multiple-unit activity in the mediodorsal nucleus of the thalamus

Rabbits received ibotenic acid lesions of the thalamic reticular nucleus or the basal forebrain, or sham lesions, and had multiple-unit recording electrodes implanted in the mediodorsal nucleus of the thalamus (MD). Animals were compared on four sessions of simple Pavlovian conditioning using a tone conditioned stimulus (CS) and periorbital electric shock unconditioned stimulus (US). Eyeblink (EB) and heart rate (HR) responses were recorded, as well as multiple-unit activity (MUA) from MD. MD MUA in sham-lesioned animals showed small but consistent increases in response to the CS. Lesions of either the basal forebrain or the thalamic reticular nucleus decreased the magnitude of the MUA changes recorded from MD and impaired acquisition of the EB conditioned response (CR). Reticular nucleus, but not basal forebrain, lesions slightly enhanced the magnitude of the HR CR. Since MD’s efferent projections are to the prefrontal cortex, these results support the idea that MD, possibly due to its forebrain-reticular afferent connections, may participate in a “response selection” function of the prefrontal cortex.

Subcortical Multiple Unit Activity Changes During Rat Male Sexual Behavior

Hernandez-Gonzalez, M., M. A. Guevara, G. Morali and M. Cervantes. Subcortical multiple unit activity changes during rat male sexual behavior. Physiol Behav 61(2) 285–291, 1997.—Multiple unit activity (MUA) was recorded from the ventral tegmental area (VTA) and mesencephalic locomotor region (MLR) during copulatory behavior of freely moving male rats. Simultaneous accelerometric recordings of the copulatory pelvic thrusting performed by the male rat were taken to precisely correlate in time the changes in MUA with well defined elements of copulation. The baseline MUA firing rates recorded in the quiet-alert condition in the VTA and in the MLR were significantly increased during pursuit of the female by the male; significantly higher MUA firing rates were found in the VTA at the 500 ms periods before and during the execution of pelvic thrusting in mount, intromission, and ejaculation responses as compared to the baseline, and returned to this value when these responses ended. The maximum MUA firing rate in the MLR was obtained during the execution of pelvic thrusting in each copulatory response, and it remained significantly elevated, as compared to the baseline, after thrusting and at the postintromission and postejaculatory genital grooming, then decreasing to basal values at the initial part of the postejaculatory interval. The fact that the highest changes in MUA were related to pelvic thrusting suggests a major participation of both structures in the execution of motor copulatory responses.

Neuronal Activity in the Medial Prefrontal Cortex during Pavlovian Eyeblink and Nictitating Membrane Conditioning

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.

Movement-related potentials within the hippocampal formation of the monkey

A series of large amplitude potentials were recorded within and surrounding the hippocampal formation in association with repetitive, self-paced hand movements in the monkey. The earliest component precedes the onset of muscle contraction by approximately 100 ms, inverts in polarity across the pyramidal cell layer of CA 3 and CA 1 and is coincident with increased local multiple unit activity (MUA). Later components, generated within the hippocampal formation, follow the muscle contraction by as much as 600 ms and are not associated with net changes in MUA. The onset of voluntary movements is often associated with desynchronization of low-frequency rhythmic hippocampal EEG patterns and these changes antecede the movement. The findings strongly suggest that the hippocampal formation is involved in the initiation and control of even simple voluntary movements in the primate.

Activity changes in nucleus reticularis gigantocellularis in relation to skilled forelimb movement in rats

Adult hooded rats were trained to reach for food pellets into a narrow plexiglass tube and the movement of the preferred forelimb was photo-electrically detected. Multiple unit activity (MUA) or single unit activity in n. reticularis gigantocellularis (NGC) was recorded during reaching. Depression of MUA was observed about the onset of the forepaw movement and lasted during its execution. There was a correlation between MUA changes and the depression of activity of individual neurons observed in a part of NGC.

Specific and non-specific multiple unit activities during pentylenetetrazol seizures in animals with mesencephalic transections

A group of cats with brain stem transection at the mesencephalic level was studied during the administration of convulsive doses of pentylenetetrazol in regard to changes in EMG multiple unit activity (MUA), as a method to determine the course of muscular convulsions and their relation with EEG and MUA changes in the motor cortex, pyramidal tract and mesencephalic and pontine reticular formations. PTZ induced significant increase in the duration of EMG tonic convulsions, lasting 3–100 times longer than the entire tonic-clonic seizure seen in intact animals after similar doses of PTZ and not accompanied by EEG or pyramidal tract ‘seizures’, but by an equally long-lasting increase in MUA of mesencephalic and pontine reticular formations. Comparing present results with those seen in intact, ‘encéphale isolé’ and ‘pretrigeminal’ preparations, it is concluded that the mesencephalon is important for both: activating tonic phase of the convulsions and the EEG changes seen in PTZ-induced seizures. It also suggests that termination of seizures is due to inhibitory influences of supramesencephalic structures.

Electrophysiological correlates of pulsatile gonadotropin release in rats.

In order to reveal the electrophysiological correlates of pulsatile LH release in ovariectomized rats, changes in multiple unit activity (MUA) in the arcuate nucleus (ARC), the medial preoptic area, the ventromedial nucleus, the anterior hypothalamic area and other areas of the brain were recorded in lightly anesthetized female rats. Rats were ovariectomized at least 7 weeks prior to the experiment. 0.1 -ml blood samples were withdrawn from a cardiac catheter at 10-min intervals during the recording in order to measure the changes in the plasma LH concentration by radioimmunoassay. The LH concentration showed pulsatile changes under continuous intravenous infusion of thiopental sodium while cortical EEG was stable throughout the experiment. The firing rate in the middle part of the ARC (8 recordings) changed in parallel with the increase in the plasma LH concentration and was abruptly raised just prior to an increase in LH secretion. The number of MUA spike discharges per minute increased to 1.5-5 times that of the basal level. MUA started to increase 2-9 min prior to the LH rise and the high level of MUA lasted for 1-5 min. The firing rate in the ARC (14 recordings) and in other areas (54 recordings) recorded did not change periodically in parallel with the increase in LH. As these changes in MUA were localized in the ARC and were not reflected in cortical EEG, they might be specific local changes distinguished from generalized systemic effects involving the whole brain. These extreme increases in MUA seem to be due to the high activity either of neurons that secrete LH-RH or those that control the secretion of LH-RH.

Oscillatory changes in multiple unit activity during rapid eye movement sleep

Multiple unit activity of the midbrain reticular formation and the hippocampus was studied in cats during the sleep-wake cycle, with particular emphasis on events occurring during rapid eye movement (REM) sleep. It was observed that most REM periods have a duration of between 2 and 8 min, and that during REM periods of 6 min or more there was a cyclic alternation between phasic REM and tonic REM. Such cyclicity was absent during REM sleep of less than 6 min. In addition, it was observed that although in general, multiple unit activity during phasic REM was higher than during tonic REM, in 31 REM periods of more than 6 min in duration, unit activity in the midbrain reticular formation and hippocampus was uncoupled. In other words, during tonic REM, hippocampal unit activity was high and reticular activity low, and vice versa during phasic REM. The same observation was made during amphetamine administration, with or without eye movements. It is suggested that in view of the lack of sensory input during REM sleep, these oscillatory and uncoupled levels of activity in different areas may represent and/or provide a kind of information processing activity during this phase of sleep. It is further suggested that REM sleep can no longer be considered a homogeneous period, because important differences exist between phasic and tonic REM sleep.

Hypothalamic electrical activity during stress

Chronic experiments on rabbits showed that excitation of the pituitary-adrenocortical system during immobilization stress is accompanied by changes in multiple unit activity in the anterior, medial, and lateral hypothalamus. Activation of the medial and inhibition of the anterior and lateral hypothalamus are observed during stress.

Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat

The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30-50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.

Ethanol-induced regional and dose-response differences in multiple-unit activity in rabbits.

Multiple-unit activity (MUA), recorded simultaneously from many brain areas, was used to detect the existence ahd location of "target sites" for ethanol action in rabbits with chronically implanted electrodes in 14 areas. Each of 12 rabbits received intraperitoneal injection of 300, 600, 900, and 1200 mg/kg of 20% ETOH and a saline control injection given in random order with at least a 4-day interval between injections. Large amounts of MUA data, recorded continuously for a 2-min pre-injection control period and a 15-min post-injection period, were quantified by a sensitive and unique technique. MUA changes did not correlate with alcohol-induced changes in the corresponding EEG for the same locus. Whereas visual inspection of the EEG did not disclose any regional differences in response to ethanol, both temporal and topographical differences in ethanol effect on MUA were observed. There were 14 histologically verified brain areas with adequate sample size for statistical evaluation of MUA response. At high doses, all brain areas were affected. Included among the brain areas which were least affected by low doseas were the caudate nucleus, septum, fornix, and medial forebrain bundle. Those areas that met the criteria for target sites of responding quickly (less than 5 min) to low doses (300 mg/kg) were: cerebellar cortex, cerebral cortex, hippocampus, lateral and medial geniculate nuclei, midbrain reticular formation, and pyriform cortex. In conjunction with the preliminary study [Brain Res. 70, 361 (1974], the data indicate that the most ethanolsensitive tissue is found in the various kinds of cortex, cerebellar and cerebral (both paleocortex and neocortex).

Local changes in multiple unit activity induced by electrochemical means in preoptic and hypothalamic areas in the female rat

Local effects of applying anodic direct current (ADC) thorugh stainless steel electrodes were studied by recording multiple unit activity with various electrode configurations in female rats under urethane anesthesia. The medial preoptic area (MPO) and anterior hypothalamic area (AHA) usually showed an increase in activity attaining its maximum by 10–25 min after ADC and lasting for 30–60 min. Some cases showed increases lasting for 2–4 h, without any consistent relationship to the current applied, brain location, or stage of estrous cycle. In the lateral preoptic area-medial forebrain bundle region only a consistent drop in activity was observed. Different current strengths induced changes in amplitude but not in duration of the increase in the MPO. No differences in responsiveness could be observed with respect to the estrous cycle. Similar increases in the MPO were obtained under pentobarbital anesthesia. These results are discussed in relation to neuroendocrine mechanisms. Caution is recommended in assuming that ADC applied through stainless steel electrodes necessarily induces a large increase in activity irrespective of the particular brain location to which it is applied. Studies regarding extradiencephalic structures are currently in progress.

Multiple unit activity in the brain correlated with induction and maintenance of pseudopregnancy in rats.

Changes in electrical activity of the brain were studied in 34 Wistar female mature rats (including 3 rats with retrochiasmatic section), following electrical stimulation of the uterine cervix on the day of estrus to induce pseudopregnancy. The macro-micro electrodes were chronically implanted into the various areas of the brain and the multiple unit activity (MUA) was recorded with no behavioral restraint. The results are summarized as follows: For several hours after the cervical stimulation (CS), the MUA in the arcuate nucleus (ARC) decreased, whereas that in the anterior hypothalamic area (AHA) and dorsomedial hypothalamic nucleus (DMH) increased. In contrast, from the 1st day until at least the 4th day, the MUA in the ARC increased, except in the frontal section 6.6 of Albe-Fessard’s atlas, while the MUA in the AHA and medial preoptic area (MPO) decreased. The MUA in the ventromedial hypothalamic nucleus (VMH) decreased immediately following or at least 2 days after the CS. From the 4th day of pseudopregnancy, the DMH, AHA, and hippocampus (HPC) showed a decrease in their MUA. CS failed to establish pseudopregnancy in rats with retrochiasmatic section. In such rats, the MUA in the ARC and AMYG showed almost no change, except for a slight and transient decrease immediately after the stimulation. The bursts of MUA characteristic of cyclic rats were not observed in the pseudo-pregnant rats; when the CS failed to induce pseudopregnancy, the characteristic bursts of MUA were suppressed for about 4 days. Afferent impulses caused by the CS may be conducted to the hypothalamic areas through anterior rather than posterior connections. The MUA changes observed for 3 or 4 days after stimulation seem to represent the brain activity that participates in the establishment of pseudopregnancy. Hormones related to the maintenance of pseudopregnancy, such as prolactin, progesterone, estrogen, and others, may cause the MUA changes on the 4th day of pseudopregnancy and, thereafter, by their feedback action.

Effect of electrical stimulation of the medial preoptic area on hypothalamic multiple unit activity in relation to LH release.

The effect of electrical stimulation of the medial preoptic area (MPO) on integrated multiple unit activity (MUA) in the arcuate nucleus (ARC) during the estrous cycle of the Wistar rat was examined with reference to the release of “the ovulating hormone” from the anterior pituitary gland. The electrical stimulation (0.5ms, 200Hz, SW, 100-500μA) was applied for 30min between 14:00 and 16:00 under pentobarbital anesthesia. 1) When the stimulus induced ovulation on the following day, MUA changes in the ARC were observed during the electrical stimulation on the day of proestrus, in contrast to their appearance after the electrical stimulation on the day of diestrus II. 2) The electrical stimulation facilitated the release of “the ovulating hormone” on the day of proestrus, while on the day of diestrus II it increased pituitary potency to induce ovulation as well, tested by an injection of a crude extract from the anterior pituitary of the experimental animals into recipients of diestrus II. 3) The circulatory level of the luteinizing hormone (LH) elevated immediately after the electrical stimulation, reached the maximum level 30 min later and returned to the control level after 60min on the day of proestrus. However, on the remaining days of the cycle it elevated immediately, reached the maximum level at 60min, but did not return to the control level even 120min after the electrical stimulation.Therefore, that the electrical stimulation of the MPO induces neural excitation of the ARC and increase of LH content in the circulation with a discrepancy in the timing throughout the cycle, indicates that the stimulation induces both synthesis and release of LH in the pituitary gland.

Changes in multiple unit activity of the brain during the estrous cycle.

Electrical activity of the brain during the critical period in the rat was examined throughout the estrous cycle, using chronically implanted macro-micro electrodes. Slight circadian rhythms were observed in the basal level of the integrated multiple unit activity (MUA) in the basal hypothalamus and forebrain limbic area. In addition to these changes, a gradual increase of MUA in the basal hypothalamus was observed during the evening of diestrus day 2, while there was no change in the forebrain limbic preoptic area. However, a characteristic elevated pattern of MUA appeared for 12 to 25 min during the critical period (2 p.m. to 4 p.m.), both in the basal hypothalamus and forebrain limbic preoptic area, i.e., in the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), medial preoptic area (MPO), septum (SEPT), amygdala (AMYG) and bed nucleus of stria terminalis (BST). The episodes of the characteristic pattern were also observed in the basal hypothalamus on the afternoons of diestrus day 2 and estrus, as well as in the forebrain limbic preoptic area on the day of estrus. To determine the possible relationship between the characteristic pattern and gonadotrophin release, electrochemical stimulation was applied to the areas of the brain where the characteristic pattern was observed during the critical period. Ovulation could be induced by stimulation of the ARC, MPO, SEPT, AMYG, and BST, but not by stimulation of the reticular formation (RF) and hippocampus (HPC). Furthermore, the results shed light on the facilitatory and inhibitory effects of progesterone on ovulation and the onset of the critical period.