Biomedical subjects

S M Brudzynski

Publications and source records attributed to S M Brudzynski.

At least 19 recordsLinked to original sources

PubMed2001

Pharmacological and behavioral characteristics of 22 kHz alarm calls in rats.

The present review is focused on the neural mechanisms and acoustic features of 22kHz alarm calls emitted by adult rats as a defensive measure in numerous behavioral situations. The alarm calls are initiated by activity of the cholinergic neurons of the laterodorsal tegmental nucleus (LDT) and a subsequent release of acetylcholine at the target areas, collectively termed as the medial cholinoceptive vocalization strip. Injection of carbachol, a predominantly muscarinic agent, into any portion of the cholinoceptive strip, or direct stimulation of the LDT, induced species-typical 22kHz calls comparable to those emitted in natural situations. The pharmacologically induced 22kHz calls contained their alarming properties for naïve rats. The 22kHz calls induced either by carbachol or by stimulation of the LDT could be antagonized by atropine, or scopolamine applied into the cholinoceptive strip. Our recent behavioral studies have shown that the combination of long call duration and constant sound frequency (20-30kHz) convey the alarming message. Anatomical and neurochemical organization of the vocalization strip and acoustic properties of the calls lead to the conclusion that 22kHz calls indicate a fundamental, negative affective state common for many behavioral situations.

Animals↗

PubMed1999

Sonographic structure of isolation-induced ultrasonic calls of rat pups.

Sonographic analysis of isolation-induced calls of 10- to 17-day-old Sprague-Dawley rat pups showed that average acoustic parameters of calls changed with pups' age. Average call duration increased with age from 80 ms to over 140 ms in 15-day-old pups. The peak frequency increased from approximately 50 kHz to an average of 64 kHz in 17-day-old pups, and the average bandwidth increased from 34 to 45 kHz in 17-day-old pups. Analysis of the sonographic structure of pup calls additionally revealed a tendency to produce two or more alternating sweeps of sound frequency in each call. Development of sweeps is the most typical feature of pup calls with a dominant call type resembling "U" or inverted "U" shape in the sonogram. Number of "U" or inverted "U" call types significantly increased with pups' age. It is concluded that pups developed and strengthened those acoustic features of distress calls which play a role in intraspecific communication and maximize pup survival.

Adaptation, Psychological↗

PubMed1998

A role of subicular and hippocampal afterdischarges in initiation of locomotor activity in rats.

The possible role of a hippocampal afterdischarge (AD) episode in eliciting locomotor movements was evaluated in freely moving rats. Electrical stimulation of either the ventral subiculum (VSB) or the hippocampal CA1 region evoked an AD of 6-50 s in duration, which was followed by an increase in locomotor activity. Similar results were also observed after unilateral injection of N-methyl-d-aspartic acid (NMDA, 0.25 microg or 1 microg), a glutamate receptor agonist, into the VSB. Locomotor activity was not observed when either electrical or chemical stimulation of the VSB, or electrical stimulation of the CA1 region did not elicit an AD. In addition, the duration of the AD was positively correlated with the number of locomotor movements induced by stimulation of VSB or CA1 region. It is suggested that the hippocampal/subicular AD may be a necessary condition to induce locomotor activity by either chemical or electrical stimulation of the hippocampus in rats.

Animals↗

PubMed1998

Mesolimbic component of the ascending cholinergic pathways: electrophysiological-pharmacological study.

The cholinergic input from the pontomesencephalic cholinergic neurons to the diencephalic and basal forebrain structures has been implicated in a number of limbically controlled overt behaviors. The cellular mechanism by which the cholinergic terminals initiate behavioral manifestations is not clear. The objective of this study was to investigate the effects of the ascending cholinergic projection from the laterodorsal tegmental nucleus (LDT) on neuronal firing in the anterior hypothalamic-medial preoptic region (AHMP), known to be involved in agonistic behavior. Experiments were performed on urethan-anesthetized rats. Iontophoretic application of carbachol (CCh) into the vicinity of single cells in the AHMP caused a dose-dependent decrease in the mean firing rate of 83% of units and an increase in 10% of units. The inhibitory effect of CCh, but not the excitatory effect, was reversed by iontophoretic pretreatment with scopolamine. The inhibition of the firing rate was repeatable for the same dose of CCh and dose dependent. Electrical stimulation of neurons in the LDT caused a comparable, current-dependent decrease in the mean firing rate of AHMP neurons that also was reversed by pretreatment of neurons in the AHMP with scopolamine. The antagonizing effects of scopolamine were reversible with time. The same units in the AHMP that inhibited their firing to stimulation of the LDT also responded with a similar inhibition to local iontophoretic CCh. Finally, the fluorescent carbocyanine dye, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide, (DiA), has been used as a retrograde axonal tracer and was injected into the recording sites immediately after the electrophysiological recordings. After 1 wk, DiA dye was found in numerous neurons in the LDT as shown by the fluorescence confocal microscopy. Results of the study suggest that LDT cholinergic neurons project and terminate in the AHMP and that their activation causes a decrease in the mean firing rate of the AHMP neurons. It is postulated that this inhibitory effect is implicated in the initiation of some of the behavioral patterns like defensive or alarm vocalization and behavioral inhibition.

Acetylcholine↗

PubMed1997

Analysis of locomotor activity in the rat: parallelism index, a new measure of locomotor exploratory pattern.

Several measures of locomotor activity in rats, including the distance covered, movement time, speed of progression, and sinuosity showed significant changes in extreme situations after prolonged preadaptation or after stimulation with I.P. amphetamine. The same measures, however, either did not change or poorly reflected the changes in locomotor activity consistent with progressive habituation in successive daily or weekly recordings. Other movement parameters, such as the average angle of turns, did not change or changed marginally, even in extreme situations. A new locomotor parameter, the parallelism index, has been proposed. It reflects the overall tendency to turn and the angular magnitude of turns. The parallelism index is not directly dependent on the distance covered by the animal, and seems to significantly reflect subtle changes in the pattern of locomotor activity that is characteristic of the exploration of an unfamiliar environment compared to the locomotor movement in frequently visited areas. A significant decrease of the parallelism index with time or repeated exposure to the cage indicates that rats perform more turns, and/or more turns under larger angles, in a more familiar or a more explored environment. It is postulated that the parallelism index decreases with the familiarity of the area being explored.

Animals↗

PubMed1997

Release of dopamine in the nucleus accumbens caused by stimulation of the subiculum in freely moving rats.

Stimulation of the ventral subiculum of the hippocampus activates the hippocampal-accumbens pathway and increases locomotor activity. Dopaminergic terminals in the nucleus accumbens have also been implicated in initiation of locomotor activity, and the release of dopamine in the nucleus accumbens is critical for locomotor responses initiated from the subiculum to occur. We have demonstrated release of dopamine in the nucleus accumbens using in vivo microdialysis after stimulation of the ventral subiculum with NMDA. Extracellular dopamine level in the nucleus accumbens was significantly increased by 40% over baseline as a result of NMDA stimulation of the ventral subiculum. This stimulation also caused more than a 40-fold increase in horizontal activity and total distance covered by the rats. Injection of saline into the subiculum caused neither a change in the dopamine level nor an increase in animal's activity. The dynamics of the measured changes in dopamine overflow correlated with the time course of locomotor changes. The results demonstrate that stimulation of the ventral subiculum causes release of dopamine in the nucleus accumbens which parallels the increase in locomotor activity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Subpallidal outputs to the nucleus accumbens and the ventral tegmental area: anatomical and electrophysiological studies.

The goal of this study was to investigate the functional organization of the subpallidal-->accumbens direct and indirect feedback loops by both anatomical and electrophysiological methods. The results of the dextran-conjugated rhodamine injections into the subpallidal area has shown three distinct projections: (1) a substantial pathway from the subpallidal area to the ventral tegmental area, (2) a more diffuse rostral projection from the subpallidal area to the core area of the nucleus accumbens, and (3) a sparse pathway projecting rostrodorsally from the subpallidal area toward the thalamic regions. Electrical or chemical stimulation of the subpallidal region, which was studied by the axonal tracer, evoked inhibitory responses in the majority (60 and 80%, respectively) of the accumbens and ventral tegmental area neurons in a standard extracellular recording study. Less than 1/3 of the accumbens or ventral tegmental area cells showed an increase in the mean firing rate. The majority (77.5%) of all responded neurons had a latency of less than 10 ms. Furthermore, injection of glutamate into the subpallidal area not only altered the firing pattern of the accumbens neurons, but also attenuated their excitatory responses elicited by the electrical stimulation of the ventral subiculum. Our results indicate that the subpallidal area plays a predominantly inhibitory role in the ventral tegmental area-accumbens-subpallidal circuitry, presumably by its GABAergic projections, and may also modulate subicular input into the nucleus accumbens.

Animals↗

PubMed1996

Involvement of the nucleus accumbens-ventral pallidal pathway in postictal behavior induced by a hippocampal afterdischarge in rats.

The hypothesis that postictal motor behaviors induced by a hippocampal afterdischarge (AD) are mediated by a pathway through the nucleus accumbens (NAC) and ventral pallidum (VP) was evaluated in freely moving rats. Tetanic stimulation of the hippocampal CA1 evoked an AD of 15-30 s and an increase in number of wet-dog shakes, face washes, rearings and locomotor activity. Bilateral injection of haloperidol (5 micrograms/side) or the selective dopamine D2 receptor antagonist, (+/-)-sulpiride (200 ng/side) before the hippocampal AD, into the NAC selectively reduced rearings and locomotor activity, but not the number of wet-dog shakes and face washes. Injection of R(+)-SCH-23390 (1 microgram/side), a D1 receptor antagonist, or rimcazole (0.4 mg/side), a sigma opioid receptor antagonist, into the NAC did not significantly alter postictal behaviors. Bilateral injection of muscimol (1 ng/side), a gamma-aminobutyric acid (GABAA) receptor agonist, into the VP before the AD significantly blocked all postictal behaviors. It is concluded that postictal locomotor activity induced by a hippocampal AD is mediated by activation of dopamine D2 receptors in the NAC and a pathway through the VP.

Animals↗

PubMed1996

Contribution of the ascending cholinergic pathways in the production of ultrasonic vocalization in the rat.

It has been well documented that cholinergic stimulation of the mediobasal forebrain structures induces 20-30 kHz ultrasonic vocalization in adult rats. If the cholinergic system plays a triggering role for ultrasonic vocalization, the question arises as to where the source of the cholinergic fibres, which innervate the mediobasal forebrain and induce vocalization, is located. In the present study, the role of the ascending cholinergic projection from the ponto-mesencephalic cholinergic nuclei to the mediobasal hypothalamic-preoptic region in production of 22 kHz calls was investigated. Cholinergic neurons were stimulated by local injection of L-glutamate and eventual vocalization was recorded by a S200 bat detector and analyzed sonographically. Intracerebral injection of L-glutamate into the laterodorsal tegmental nucleus induced short latency, 20-30 kHz ultrasonic calls. Sound frequency (pitch) and single call duration of the L-glutamate-induced vocalization did not differ from those obtained by cholinergic stimulation of the mediobasal hypothalamic-preoptic region with carbachol. However, L-glutamate stimulation of the laterodorsal tegmental nucleus was ineffective or less effective in 70% of responses, when the terminal fields in the mediobasal hypothalamic-preoptic region were pretreated with scopolamine, a muscarinic antagonist. The results demonstrate that the ascending cholinergic projection from the laterodorsal tegmental nucleus plays a triggering role for 20-20 kHz vocalization in adult rats.

Animals↗

PubMed1996

C-Fos immunohistochemical localization of neurons in the mesencephalic locomotor region in the rat brain.

The projection from the limbic system via the subpallidal region to the mesencephalic locomotor region is implicated in limbic-motor integration. The goal of this study was to visualize neurons of the mesencephalic locomotor region which are active during locomotor activity induced by the disinhibition of the subpallidal region. The subpallidal region was disinhibited by picrotoxin, which antagonizes the effects of GABA. The unilateral injection of picrotoxin into the subpallidal region caused a significant increase in locomotor activity. Active tegmental neurons were subsequently visualized by immunocytochemical staining of c-Fos protein. There were significantly more immunostained neurons in the picrotoxin-injected animals than in the saline-treated rats. Heavily stained neuronal nuclei, prevailing on the brain side ipsilateral to the injection of picrotoxin, were localized within a narrow strip of tissue which stretched from the ventrolateral periaqueductal gray (including the dorsal raphe), the cuneiform nucleus, through the region of the dorsal tegmental bundle to the pedunculopontine nucleus. There were 3.5 times more immunostained neurons in the cuneiform/pedunculopontine region and 2.5 times more stained neurons in the periaqueductal region of the picrotoxin-injected rats, as compared to the saline group. This strip of immunostained cells represents neurons which are involved in the initiation and maintenance of locomotor activity due to subpallidal activation (predominantly pedunculopontine and cuneiform nuclei), as well as neurons possibly involved in the inhibition of locomotor activity (ventrolateral periaqueductal gray) and other feedback regulations. This study will help identify the neuronal pool involved in coupling the motivational commands with the locomotor system for execution of behaviour.

Animals↗

PubMed1995

Mesolimbic dopamine terminals and locomotor activity induced from the subiculum.

The role of the mesolimbic dopamine terminals in the nucleus accumbens in the initiation of locomotion in rats was studied. Locomotor activity was initiated by activation of the excitatory input from the ventral subiculum to the nucleus accumbens with NMDA. Measurements of locomotor activity, induced by unilateral administration of NMDA into the ventral subiculum, were compared before and after destruction of the mesolimbic dopamine terminals in the nucleus accumbens. The dopamine terminals were destroyed by injection of 6-OHDA into the ventral tegmental area which projects to the nucleus accumbens. Injection of NMDA into the ventral subiculum caused an almost four-fold increase in locomotor activity. However, this increase was abolished after the destruction of the mesolimbic dopamine terminals in the nucleus accumbens. The results suggest that the mesolimbic dopamine terminals are essential in transmitting subicular signals to the output neurones within the nucleus accumbens.

Animals↗

PubMed1995

Behavioural responses of laboratory rats to playback of 22 kHz ultrasonic calls.

It has been demonstrated that cholinergic stimulation of the anterior hypothalamic-preoptic region induces 22 kHz ultrasonic vocalization in rats. Acoustic features of the cholinergically induced vocalization did not differ from those of 22 kHz calls emitted in natural situations and, therefore, could have a behavioural significance for other conspecifics. The 22 kHz calls induced by intracerebral injection of carbachol were played back to rats and their responses were compared with responses to playback of 22 kHz calls induced by tactile stimuli and to those with background noise. Animal responses were measured by an accelerometric sensor as an average ergometric activity. The average activity count was not changed during presentation of acoustic stimuli, however, striking differences were found in animal responses immediately after discontinuation of the sound. Activity of the rats consistently and significantly decreased after presentation of 22 kHz calls induced by tactile stimuli or by injection of carbachol. Animal responses to calls induced by carbachol were indistinguishable from responses to calls induced by tactile stimuli. No significant changes in the general activity of the animals were observed after presentation of the background noise or during the sessions without stimuli. The results demonstrate that carbachol-induced ultrasonic calls have behavioural significance for other conspecifics and could serve as an alarm call in a similar way to naturally produced 22 kHz vocalization.

Acoustic Stimulation↗

PubMed1995

Cholinergic mechanisms in generalized seizures: importance of the zona incerta.

OBJECTIVE: Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain. METHODS: Carbachol was injected directly into the brain in a dose of 1 or 3 micrograms. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe. RESULTS: Injections of high dose carbachol (3 micrograms) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 microgram) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta. CONCLUSIONS: Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.

Animals↗

PubMed1995

Regional specificity of the emotional-aversive response induced by carbachol in the cat brain: a quantitative mapping study.

In this paper, the emotional-aversive response induced by intracerebral injection of carbachol has been studied in cats by recording their vocalization as an index of emotional behavior. The carbachol-induced responses were quantitatively mapped in the basal forebrain and diencephalic regions using the cumulative time of the animal's vocalization as a measure of response. The areas inducing the emotional- aversive response extended along two axes: 1. longitudinally along the neuraxis, from the reticular formation through the hypothalamus to the rostro-basal forebrain; and 2. vertically along the fornix, from the mediobasal hypothalamus to the septal area. The highest magnitude of the response (vocalization time) was obtained from a strip of tissue extending from the septum and preoptic area to the dorsal perifornical area, the dorsomedial hypothalamic nucleus, the paraventricular nucleus and the periventricular stratum. The pattern of distribution of reactive and nonreactive sites showed anatomic specificity, with the highest sensitivity found within the close periventricular tissue of the third ventricle. It is suggested that carbachol mapping selectively delineates the muscarinic cholinoceptive portion of the aversive, emotional brain system.

Animals↗

PubMed1994

Ultrasonic vocalization induced by intracerebral carbachol in rats: localization and a dose-response study.

It has been recently demonstrated that application of a cholinergic agonist, carbachol, into the anterior hypothalamic-preoptic area in the rat can induce 22 kHz ultrasonic vocalization. Functional mapping of the response in the forebrain and diencephalic regions of the rat brain, as well as the relationship between the dose of carbachol and the multi-parameter recording of vocalization are analyzed in the present study. Direct pressure injection of carbachol into the brain of adapted rats induced a 22 kHz ultrasonic vocalization from a limited region of the anterior hypothalamic-preoptic area and the vicinity of the septum. The response was antagonized by a local pretreatment with atropine and could not be induced by injections of saline vehicle or by handling. Measurements of summed duration of individual calls and response duration showed a typical dose-response relationship for 32-fold range of carbachol doses with ED50 = 0.73 micrograms (4.0 nmol). The increasing dosage of carbachol did not influence the frequency of emitted ultrasounds. On the other hand, the sound intensity increased and the bandwidth decreased with the increasing dosage of carbachol. The mean duration of single calls was also significantly decreased with the carbachol dosage. However, higher doses of carbachol decreased the number of short calls (100-150 ms) but increased the number of longer calls (300-400 ms). The duration of individual calls appeared to be a sensitive index of the response intensity. The results suggest that the cholinergic input into the mediobasal forebrain may play a physiological role in initiating and emitting the 22 kHz ultrasonic vocalization in rats, and that changes in call duration, intensity and bandwidth may be involved in conveying information for conspecifics.

Animals↗

PubMed1994

Involvement of M1 muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain.

The present study was designed to determine the types of acetylcholine receptors involved in the initiation of epileptic seizures from the zona incerta and surrounding structures by cholinergic stimulation in rats. Unilateral intracerebral microinjection of the mixed muscarinic and nicotinic agonist carbachol (3 micrograms) produced generalized seizures in 12 of 20 rats studied. Local pretreatment with equimolar doses of acetylcholine receptor antagonists was used as a method of determining the receptor type involved in the initiation of cholinergically induced seizures in the rat diencephalon. Pretreatment with the M1 muscarinic receptor antagonist, pirenzepine (7 micrograms), abolished carbachol-induced seizures in 91% of the animals tested. The M2 muscarinic receptor antagonist, methoctramine (12 micrograms) and the nicotinic receptor antagonist, mecamylamine (3 micrograms), were relatively ineffective in antagonizing seizures in 9% and 27%, respectively. The results suggest that M1 muscarinic receptors are preferentially involved in the initiation of generalized epileptic seizures in the basal diencephalon of the rat.

Animals↗

PubMed1994

High-frequency ultrasonic vocalization induced by intracerebral glutamate in rats.

Direct injection of glutamate, a neuroexcitatory agent, into the anterior hypothalamic-preoptic area of the rat brain induced ultrasonic vocalization. This vocalization was characterized by short-duration calls (below 60 ms) of high sound frequency (pitch), mostly above 40 kHz, and was similar to the known 50-kHz vocalization observed in natural situations. The glutamate-induced vocalization was dose dependent within the dose range of 16.9-67.6 micrograms and was antagonized by local pretreatment with MK-801, an NMDA antagonist. The increasing dosage of glutamate induced more calls and had a significant influence on frequency and intensity of emitted ultrasound. The average sound frequency increased whereas the mean sound intensity decreased with the dosage of glutamate. On the other hand, the mean duration of a single call and the bandwidth did not significantly change with doses of glutamate. Injection of carbachol, a muscarinic cholinomimetic agent, into the same brain sites as glutamate, induced a different type of ultrasonic vocalization with low sound frequency and long call duration, known as 22-kHz calls. The results suggest that high sound frequency, short-duration calls (50 kHz) and low sound frequency, long-duration calls (22 kHz) have different neurophysiological and neurochemical mechanisms.

Animals↗

PubMed1994

Chromogranin A applied to the nucleus accumbens decreases locomotor activity induced by activation of the mesolimbic dopaminergic system in the rat.

The aim of the study was to obtain supporting evidence, using a behavioral paradigm, of the hypothesis that chromogranin A attenuates transmitter release in the CNS. We studied the effects of chromogranin A injected into the nucleus accumbens on locomotor activity triggered by application of picrotoxin into the ventral tegmental area of rats. Injection of picrotoxin into the ventral tegmental area, which is known to disinhibit dopaminergic mesolimbic neurons, caused a significant increase in horizontal activity. Distance covered during locomotion and movement time increased more than twofold, whereas stereotypy time and number, indices of nonlocomotor behavior, were not significantly affected by picrotoxin. Pressure injection of chromogranin A into the nucleus accumbens prior to injection of picrotoxin into the ventral tegmental area prevented these locomotor effects and had little or no effect on nonlocomotor behavior. Similarly, the picrotoxin-induced activity was prevented by injecting cobalt chloride into the nucleus accumbens. The results show that chromogranin A has an attenuating effect, either directly or indirectly, on dopaminergic neurotransmission in the nucleus accumbens that can be exemplified by inhibiting picrotoxin-induced locomotor activity. Further studies are needed to determine the mechanism of chromogranin A action in the nucleus accumbens.

Animals↗