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The Journal of Neuroscience : the... Aug 2020The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes...
The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia-thalamocortical loop. In this study, we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, that the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance. The mediodorsal nucleus (MD) of the thalamus is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.
Topics: Animals; Conditioning, Operant; GABA-A Receptor Agonists; Male; Mediodorsal Thalamic Nucleus; Mice, Inbred C57BL; Muscimol; Optogenetics; Psychomotor Performance; Reward; Time Perception
PubMed: 32493711
DOI: 10.1523/JNEUROSCI.0695-20.2020 -
Hippocampus Apr 2018The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral midline...
The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral midline thalamus is an important anatomical link between the HF and mPFC, and as such is crucially involved in SWM functions that recruit both structures. Little is known, however, regarding the role of RE in other behaviors mediated by this circuit. In the present study, we examined the role of RE in spatial working memory and executive functioning following reversible inactivation of RE with either muscimol or procaine. Rats were implanted with an indwelling cannula targeting RE and trained in a delayed nonmatch to sample spatial alternation T-maze task. For the task, sample and choice runs were separated by moderate or long delays (30, 60, and 120 s). Following asymptotic performance, rats were tested following infusions of drug or vehicle. Muscimol infused into RE impaired SWM at all delays, whereby procaine only impaired performance at the longest delays. Furthermore, RE inactivation with muscimol produced a failure in win-shift strategy as well as severe spatial perseveration, whereby rats persistently made re-entries into incorrect arms during correction trials, despite the absence of reward. This demonstrated marked changes in behavioral flexibility and response strategy. These results strengthen the role of nucleus reuniens as a pivotal link between hippocampus and prefrontal cortex in cognitive and executive functions and suggest that nucleus reuniens may be a potential target in the treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity disorder, addiction, and obsessive-compulsive disorder, whose symptoms are defined by hippocampal-prefrontal dysfunctions.
Topics: Animals; Central Nervous System Agents; Executive Function; Male; Maze Learning; Memory, Short-Term; Muscimol; Procaine; Rats, Long-Evans; Spatial Memory; Time Factors; Ventral Thalamic Nuclei
PubMed: 29357198
DOI: 10.1002/hipo.22831 -
Frontiers in Neural Circuits 2021It is well known that communication between the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC) is critical for various cognitive and behavioral...
It is well known that communication between the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC) is critical for various cognitive and behavioral functions. However, the exact role of these structures in spatial coordination remains to be clarified. Here we sought to determine the involvement of the mPFC and the vHPC in the spatial retrieval of a previously learned active place avoidance task in adult male Long-Evans rats, using a combination of unilateral and bilateral local muscimol inactivations. Moreover, we tested the role of the vHPC-mPFC pathway by performing combined ipsilateral and contralateral inactivations. Our results showed not only bilateral inactivations of either structure, but also the combined inactivations impaired the retrieval of spatial memory, whereas unilateral one-structure inactivations did not yield any effect. Remarkably, muscimol injections in combined groups exerted similar deficits, regardless of whether the inactivations were contralateral or ipsilateral. These findings confirm the importance of these structures in spatial cognition and emphasize the importance of the intact functioning of the vHPC-mPFC pathway.
Topics: Animals; Hippocampus; Male; Muscimol; Prefrontal Cortex; Rats; Rats, Long-Evans; Spatial Memory
PubMed: 33994956
DOI: 10.3389/fncir.2021.634533 -
Polish Journal of Pharmacology 2002Muscimol, a selective agonist of GABA-A receptors, causes changes in behavioral activity. Hypoxia interferes with the GABAergic system and with the functions of GABA-A... (Comparative Study)
Comparative Study
Muscimol, a selective agonist of GABA-A receptors, causes changes in behavioral activity. Hypoxia interferes with the GABAergic system and with the functions of GABA-A receptors. We used muscimol in Wistar rats to estimate its influence on locomotor activity in the open field test as well as on the processes of consolidation and retrieval, evaluated in the test of passive conditioned reflexes. Anxiolytic activity was examined in the elevated "plus" maze in physiological state and after hypoxia-induced amnesia. Following intraperitoneal administration of muscimol (1 mg/kg, ip), the animals showed a decrease in motility, in retrieval of skill reflexes and in a number of entries into open and closed arms in the elevated plus "maze". In animals exposed to hypoxia, we observed reduced motility in the open field, inhibition of retrieval and consolidation of passive conditioned reflexes, shortened time of sojourn in open arms and decreased number of entries into open and closed arms. In the group of animals which underwent hypoxia and then received muscimol, we observed no effect of hypoxia on muscimol activity in the open field test, except rearing when muscimol action was significantly reduced. Muscimol improved consolidation but not retrieval in comparison with the hypoxic saline-treated group of rats. In the elevated "plus" maze test, treatment of rats with muscimol after hypoxia significantly prolonged the time spent in open arms and increased the number of entries into open arms, while shortened the time spent in closed arms. In conclusion, muscimol in hypoxia-exposed group of rats exerted beneficial effect on consolidation in passive avoidance situation and exerted anxiolytic activity. Changes in the activity of muscimol under hypoxia may have significant clinical implications.
Topics: Animals; Avoidance Learning; Behavior, Animal; Exploratory Behavior; Female; GABA Agonists; Hypoxia; Maze Learning; Motor Activity; Muscimol; Rats; Rats, Wistar; Receptors, GABA-A
PubMed: 12593529
DOI: No ID Found -
PloS One 2023The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions...
The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5μL saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.
Topics: Rats; Female; Male; Animals; Basolateral Nuclear Complex; Oxytocin; Insular Cortex; Muscimol; Social Behavior
PubMed: 37797037
DOI: 10.1371/journal.pone.0281794 -
Acta Pharmacologica Sinica Feb 2013To investigate the effects of microinjection of the GABA(A) receptor agonist muscimol into cerebellar fastigial nucleus (FN) on stress-induced gastric mucosal damage and...
AIM
To investigate the effects of microinjection of the GABA(A) receptor agonist muscimol into cerebellar fastigial nucleus (FN) on stress-induced gastric mucosal damage and the underlying mechanism in rats.
METHODS
Stress-induced gastric mucosal damage was induced in adult male SD rats by restraining and immersing them in cold water for 3 h. GABA(A) receptor agonist or antagonist was microinjected into the lateral FN. The decussation of superior cerebellar peduncle (DSCP) was electrically destroyed and the lateral hypothalamic area (LHA) was chemically ablated by microinjection of kainic acid. The pathological changes in the gastric mucosa were evaluated using TUNEL staining, immunohistochemistry staining and Western blotting.
RESULTS
Microinjection of muscimol (1.25, 2.5, and 5.0 μg) into FN significantly exacerbated the stress-induced gastric mucosal damage in a dose-dependent manner, whereas microinjection of GABA(A) receptor antagonist bicuculline attenuated the damage. The intensifying effect of muscimol on gastric mucosal damage was abolished by electrical lesion of DSCP or chemical ablation of LHA performed 3 d before microinjection of muscimol. Microinjection of muscimol markedly increased the discharge frequency of the greater splanchnic nerve, significantly increased the gastric acid volume and acidity, and further reduced the gastric mucosal blood flow. In the gastric mucosa, further reduced proliferation cells, enhanced apoptosis, and decreased anti-oxidant levels were observed following microinjection of muscimol.
CONCLUSION
Cerebellar FN participates in the regulation of stress-induced gastric mucosal damage, and cerebello-hypothalamic circuits contribute to the process.
Topics: Animals; Apoptosis; Bicuculline; Cerebellar Nuclei; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Gastric Mucosa; Hypothalamic Area, Lateral; Male; Microinjections; Muscimol; Rats; Rats, Sprague-Dawley; Stress, Physiological
PubMed: 23247592
DOI: 10.1038/aps.2012.152 -
Journal of Korean Medical Science Oct 2011Glycine and γ-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are...
Glycine and γ-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABA(A) receptor agonist), baclofen (a GABA(B) receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.
Topics: Animals; Baclofen; Drug Delivery Systems; GABA Agonists; GABA Antagonists; Glycine; Hot Temperature; Hyperalgesia; Injections, Spinal; Male; Mice; Mice, Inbred ICR; Muscimol; Pain Threshold; Random Allocation; Strychnine; gamma-Aminobutyric Acid
PubMed: 22022192
DOI: 10.3346/jkms.2011.26.10.1371 -
Polish Journal of Pharmacology 2002Alcohol-naive high- (Warsaw High Preferring; WHP) and low- (Warsaw Low Preferring; WLP) preferring lines of rat were studied to determine the distribution and density of... (Comparative Study)
Comparative Study
Alcohol-naive high- (Warsaw High Preferring; WHP) and low- (Warsaw Low Preferring; WLP) preferring lines of rat were studied to determine the distribution and density of [3H]muscimol binding sites in the brain using quantitative autoradiography. The results have shown no difference in the density of [3H]muscimol binding sites in the cingulate and frontal cortex, dorsal and ventral striatum, lateral and medial septum, caudate-putamen, nucleus accumbens in the both lines of animals. In the separate experiments, the levels of neurotransimitters were measured in the frontal cortex, hippocampus and striatum of the WHP and WLP rats. The content of dopamine was significantly lower in the striatum of the WHP rats as compared to the WLP animals. The levels of serotonin and noradrenaline were without any important differences in the examined structures of both lines of rats.
Topics: Alcohol Drinking; Animals; Binding Sites; Brain; Crosses, Genetic; Muscimol; Neurotransmitter Agents; Rats; Rats, Inbred Strains; Rats, Wistar; Species Specificity; Tritium
PubMed: 12398153
DOI: No ID Found -
Journal of Neurophysiology Dec 2001We investigated the effects of linear perspective and binocular disparity, as monocular and binocular depth cues, respectively, on the response of...
We investigated the effects of linear perspective and binocular disparity, as monocular and binocular depth cues, respectively, on the response of surface-orientation-selective (SOS) neurons in the caudal part of the lateral bank of the intraparietal sulcus (area CIP). During the single-unit recording, monkeys were required to perform the delayed-matching-to-sample (successive same/different discrimination) of discriminating surface orientation in stereoscopic computer graphics. Of 211 visually responsive neurons, 66 were intensively tested using the solid-figure stereogram (SFS) of a square plate with both disparity and perspective cues (D+P condition), and 62 of these were identified as SOS neurons for responding selectively to the orientation of stimuli. All these neurons were further tested using a solid figure with perspective cues alone (P-only condition), and 58% (36/62) of these showed selective response to the orientation of the stimuli. Of the 62 SOS neurons, 35 neurons were also tested using SFS with disparity cues alone (D-only condition) in addition to the D+P and P-only conditions. We classified these 35 neurons into four groups by comparing the response selectivity under the P-only and D-only conditions. More than one-half of these (19/35) were sensitive to both perspective and disparity cues (DP neurons), and nearly one-third (11/35) of these were sensitive to disparity cues alone (D neurons), but a few (2/35) were sensitive to perspective cues alone (P neurons). The remaining (3/35) neurons exhibited orientation selectivity only when both cues were present. In DP neurons, the preferred orientation under the D+P condition was correlated to those under the D-only and P-only conditions, and the response magnitude under the D+P condition was greater than those under the D-only and P-only conditions, suggesting the integration of both cues for the perception of surface orientation. However, in these neurons, the orientation tuning sharpness under the D+P and D-only conditions was higher than that under the P-only condition, suggesting the dominance of disparity cues. After the single-unit recording experiments, muscimol was microinjected into the recording site to temporarily inactivate its function. In all three effective cases out of six microinjection experiments, discrimination of a three-dimensional (3D) surface orientation was impaired when disparity cues alone were present. In only one effective case, when a relatively large amount of muscimol was microinjected, discrimination of a 3D surface orientation was impaired even when both disparity and perspective cues were present. These results suggest that linear perspective is an important cue for representations of a 3D surface of SOS neurons in area CIP, although it is less effective than binocular disparity, and that both of these depth cues may be integrated in area CIP for the perception of surface orientation in depth.
Topics: Algorithms; Animals; Cues; Depth Perception; Discrimination, Psychological; Eye Movements; GABA Agonists; Macaca; Male; Microinjections; Muscimol; Neurons; Orientation; Parietal Lobe; Photic Stimulation; Stereotaxic Techniques; Vision Disparity; Vision, Binocular; Vision, Monocular
PubMed: 11731542
DOI: 10.1152/jn.2001.86.6.2856 -
Journal of Neurophysiology Oct 2013Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in...
Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys. We used unilateral injections of the GABAA agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic monkey S1 with ≈ 4° of exotropia; 5 injections in esotropic monkey S2 with ≈ 34° of esotropia) and the PIN (3 injections in monkey S1). cFN inactivation induced horizontal saccade dysmetria in all experiments (mean 39% increase in ipsilesional saccade gain and 26% decrease in contralesional gain). Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN inactivation induced a divergent change in eye alignment in both monkeys, with exotropia increasing by an average of 9.8° in monkey S1 and esotropia decreasing by an average of 11.2° in monkey S2 (P < 0.001). Unilateral PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward saccades by 13% and also induced a convergent change in eye alignment, reducing exotropia by an average of 2.7° (P < 0.001). We conclude that cFN/PIN influences on conjugate eye movements in strabismic monkeys are similar to those postulated in normal monkeys and cFN/PIN play important and complementary roles in maintaining the steady-state misalignment in strabismus.
Topics: Animals; Cerebellar Nuclei; Macaca mulatta; Muscimol; Saccades; Strabismus; Vision, Binocular
PubMed: 23883862
DOI: 10.1152/jn.00233.2013