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Neurobiology of Learning and Memory Mar 2021The insular cortex (IC) is notably implicated in emotional and cognitive processing; however, little is known regarding to what extent its two main subregions play...
The insular cortex (IC) is notably implicated in emotional and cognitive processing; however, little is known regarding to what extent its two main subregions play functionally distinct roles on memory consolidation of conditioned fear tasks. Here we verified the effects of temporary functional inactivation of the anterior (aIC) and posterior IC (pIC) on contextual and tone fear memory. Rats received post-training bilateral infusions of the GABA receptor agonist muscimol into either the aIC or pIC and were tested 48 and 72 h after the delay tone fear conditioning session to assess the background contextual (CFC) and tone (TFC) fear conditioning, respectively. Inactivation of the aIC during memory consolidation did not affect fear memory for CFC or TFC. On the other hand, post-training inactivation of the pIC impaired TFC but not CFC. Our findings indicate that the pIC is a necessary part of the neural circuitry related to the consolidation of cued-fear memories.
Topics: Acoustic Stimulation; Animals; Cerebral Cortex; Conditioning, Classical; Fear; GABA-A Receptor Agonists; Memory Consolidation; Muscimol; Rats
PubMed: 33581316
DOI: 10.1016/j.nlm.2021.107402 -
Acta Neurobiologiae Experimentalis 1990Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male...
Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male albino rats. Electrical activity of these regions was recorded electrographically before and following intracranial injection (ICI) of GABA, muscimol and picrotoxin. In another set of animals, food intake and water intake were also measured. The activity of the ventromedial hypothalamus changed from slow to fast after ICI of GABA and picrotoxin and fast to slow after muscimol. The activity of the lateral hypothalamus changed from slow to fast with ICI of muscimol and picrotoxin and from fast to slow with GABA, while that of the paraventricular hypothalamic nucleus changed from slow to fast with ICI GABA and fast to slow with muscimol and picrotoxin. ICI of GABA into VMH and LHA and muscimol in VMH, LHA and PVH caused a decrease in food intake. Water intake was also decreased after ICI of GABA in PVH and muscimol in LHA and PVH. On the opposite picrotoxin increased food intake in VMA and LHA and water intake in PVH. The possible interaction of GABAergic drugs with the areas of the brain controlling feeding and drinking is being discussed.
Topics: Action Potentials; Animals; Drinking Behavior; Feeding Behavior; Hypothalamus; Male; Microinjections; Muscimol; Picrotoxin; Rats; Rats, Inbred Strains; gamma-Aminobutyric Acid
PubMed: 2220435
DOI: No ID Found -
Hippocampus Jun 2023The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility...
The hippocampus is a critical component of a mammalian spatial navigation system, with the firing sequences of hippocampal place cells during sleep or immobility constituting a "replay" of an animal's past trajectories. A novel spatial navigation task recently revealed that such "replay" sequences of place fields can also prospectively map onto imminent new paths to a goal that occupies a stable location during each session. It was hypothesized that such "prospective replay" sequences may play a causal role in goal-directed navigation. In the present study, we query this putative causal role in finding only minimal effects of muscimol-induced inactivation of the dorsal and intermediate hippocampus on the same spatial navigation task. The concentration of muscimol used demonstrably inhibited hippocampal cell firing in vivo and caused a severe deficit in a hippocampal-dependent "episodic-like" spatial memory task in a watermaze. These findings call into question whether "prospective replay" of an imminent and direct path is actually necessary for its execution in certain navigational tasks.
Topics: Animals; Goals; Muscimol; Prospective Studies; Spatial Navigation; Hippocampus; Mammals
PubMed: 36798045
DOI: 10.1002/hipo.23497 -
Neuroscience Letters Apr 2019Tonic immobility (TI) is a temporary state of profound motor inhibition associated with great danger as the attack of a predator. Previous studies carried out in our...
Tonic immobility (TI) is a temporary state of profound motor inhibition associated with great danger as the attack of a predator. Previous studies carried out in our laboratory evidenced high Fos-IR in the posteroventral region of the medial nucleus of the amygdala (MEA) after induction of the TI response. Here, we investigated the effects of GABA and GABA of the MEA on TI duration. Intra-MEA injections of the GABA agonist muscimol and GABA agonist baclofen reduced TI response, while intra-MEA injections of the GABA antagonist bicuculline and GABA antagonist phaclofen increased the TI response. Moreover, the effects observed with muscimol and baclofen administrations into MEA were blocked by pretreatment with bicuculline and phaclofen (at ineffective doses per se). Finally, the activation of GABA and GABA receptors in the MEA did not alter the spontaneous motor activity in the open field test. These data support the role of the GABAergic system of the MEA in the modulation of innate fear.
Topics: Animals; Baclofen; Bicuculline; Corticomedial Nuclear Complex; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; Guinea Pigs; Immobility Response, Tonic; Male; Microinjections; Motor Activity; Muscimol
PubMed: 30753913
DOI: 10.1016/j.neulet.2019.01.054 -
The Journal of Physiology Feb 19951. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central...
1. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central administration of a GABAA receptor agonist (muscimol) and antagonist (bicuculline) on the milk ejection reflex in the urethane-anaesthetized rat. 2. Intracerebroventricular (i.c.v.) injection of both muscimol (n = 17), at doses of 5, 10 and 20 ng, and bicuculline (n = 15), at doses of 0.01, 0.1 and 0.3 microgram, inhibited the milk ejection reflex in a dose-dependent manner. The bicuculline-induced inhibition was accompanied by desynchronization of the electroencephalogram and, at the highest dose, by alteration in the sensitivity of the mammary gland to oxytocin. No significant effect on the milk ejection reflex was seen with i.c.v. isotonic saline (n = 5). 3. Injection of 20 (n = 5) or 40 ng (n = 2) muscimol or 0.1 microgram bicuculline (n = 5) i.c.v. did not significantly alter the rise in intramammary pressure evoked by electrical stimulation of the neurohypophysis. 4. Bilateral 400 nl microinfusions directly into the supraoptic nuclei of either muscimol (20-100 ng microliter(-1); n = 10) or bicuculline (0.15 micrograms microliter(-1); n = 5) [corrected] resulted in an inhibition of the milk ejection reflex, which was not accompanied by desynchronization of the electroencephalogram. 5. The effects of i.c.v. injections of muscimol (15 and 20 ng) and bicuculline (0.01, 0.12 and 0.3 microgram) on the electrical activity of twenty-seven antidromically identified supraoptic magnocellular neurones were examined. Both compounds resulted in an inhibition of the background firing of oxytocinergic and vasopressinergic cells, and delayed the occurrence of high frequency bursts in oxytocin neurones. In five supraoptic neurones, bicuculline induced a transient activation before inhibition. 6. The powerful inhibitory action on the milk ejection reflex of both muscimol and bicuculline provides evidence for the importance of GABA neurones in maintaining the functional integrity of the mechanisms which allow the intermittent and pulsatile release of oxytocin during suckling.
Topics: Action Potentials; Animals; Bicuculline; Electric Stimulation; Electroencephalography; Female; Injections, Intraventricular; Mammary Glands, Animal; Milk Ejection; Muscimol; Neurons; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Wistar; Receptors, GABA; Reflex; Supraoptic Nucleus
PubMed: 7776233
DOI: 10.1113/jphysiol.1995.sp020579 -
Journal of Visualized Experiments : JoVE Nov 2019This microinjectrode system is designed for drug infusion, electrophysiology, and delivery and retrieval of experimental probes, such as microelectrodes and nanosensors,...
This microinjectrode system is designed for drug infusion, electrophysiology, and delivery and retrieval of experimental probes, such as microelectrodes and nanosensors, optimized for repeated use in awake, behaving animals. The microinjectrode system can be configured for multiple purposes: (1) simple arrangement of the cannula for placement of an experimental probe that would otherwise be too fragile to penetrate the dura mater, (2) microfluidic infusion of a drug, either independently or coupled to a cannula containing an experimental probe (i.e., microelectrode, nanosensor). In this protocol we explain the step by step construction of the microinjectrode, its coupling to microfluidic components, and the protocol for use of the system in vivo. The microfluidic components of this system allow for delivery of volumes on the nanoliter scale, with minimal penetration damage. Drug infusion can be performed independently or simultaneously with experimental probes such as microelectrodes or nanosensors in an awake, behaving animal. Applications of this system range from measuring the effects of a drug on cortical electrical activity and behavior, to understanding the function of a specific region of cortex in the context of behavioral performance based on probe or nanosensor measurements. To demonstrate some of the capabilities of this system, we present an example of muscimol infusion for reversible inactivation of the frontal eye field (FEF) in rhesus macaque during a working memory task.
Topics: Animals; Electrophysiological Phenomena; Macaca mulatta; Memory; Microelectrodes; Microfluidics; Muscimol; Pharmaceutical Preparations; Saccades; Task Performance and Analysis; Visual Fields; Wakefulness
PubMed: 31789311
DOI: 10.3791/60365 -
Brain Research Dec 2022Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male...
Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male and female rats with spared nerve injury (SNI) model of neuropathy. SNI induced mechanical hypersensitivity that was stronger in females. Reversible blocking of the CeA with muscimol (GABA receptor agonist) induced a reduction of mechanical hypersensitivity that did not differ between males and females. Following spinal co-administration of atipamezole (α-adrenoceptor antagonist), the reduction of mechanical hypersensitivity by CeA muscimol was attenuated more in males than females. In contrast, following spinal co-administration of raclopride (dopamine D2 receptor antagonist) the reduction of hypersensitivity by CeA muscimol was attenuated more in females than males. The reduction of mechanical hypersensitivity by CeA muscimol was equally attenuated in males and females by spinal co-administration of WAY-100635 (5-HT receptor antagonist) or bicuculline (GABA receptor antagonist). The CeA muscimol induced attenuation of ongoing pain-like behavior (conditioned place preference test) that was reversed by spinal co-administration of atipamezole in both sexes. The results support the hypothesis that CeA contributes to mechanical hypersensitivity and ongoing pain-like behavior in SNI males and females. Disinhibition of descending controls acting on spinal α-adrenoceptors, 5-HT, dopamine D2 and GABA receptors provides a plausible explanation for the reduction of mechanical hypersensitivity by CeA block in SNI. The involvement of spinal dopamine D2 receptors and α-adrenoceptors in the CeA muscimol-induced reduction of mechanical hypersensitivity is sexually dimorphic, unlike that of spinal α-adrenoceptors in the reduction of ongoing neuropathic pain.
Topics: Female; Rats; Male; Animals; Muscimol; Receptors, GABA-A; Neuralgia; Amygdala; Receptors, Neurotransmitter; GABA-A Receptor Antagonists; Receptors, Adrenergic
PubMed: 36265669
DOI: 10.1016/j.brainres.2022.148128 -
The Journal of Comparative Neurology Dec 2021The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive...
The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive cortico-pulvino-cortical input-output loops. Neurophysiological studies have suggested a role for these transthalamic pathways in regulating information transmission between cortical areas. However, evidence for a causal role of the pulvinar in regulating cortico-cortical interactions is sparse and it is not known whether pulvinar's influences on cortical networks are task-dependent or, alternatively, reflect more basic large-scale network properties that maintain functional connectivity across networks regardless of active task demands. In the current study, under passive viewing conditions, we conducted simultaneous electrophysiological recordings from ventral (area V4) and dorsal (lateral intraparietal area [LIP]) nodes of macaque visual system, while reversibly inactivating the dorsal part of the lateral pulvinar (dPL), which shares common anatomical connectivity with V4 and LIP, to probe a causal role of the pulvinar. Our results show a significant reduction in local field potential phase coherence between LIP and V4 in low frequencies (4-15 Hz) following muscimol injection into dPL. At the local level, no significant changes in firing rates or LFP power were observed in LIP or in V4 following dPL inactivation. Synchronization between pulvinar spikes and cortical LFP phase decreased in low frequencies (4-15 Hz) both in LIP and V4, while the low frequency synchronization between LIP spikes and pulvinar phase increased. These results indicate a causal role for pulvinar in synchronizing neural activity between interconnected cortical nodes of a large-scale network, even in the absence of an active task state.
Topics: Animals; Electrophysiology; Macaca; Muscimol; Pulvinar; Visual Cortex; Visual Pathways
PubMed: 34013540
DOI: 10.1002/cne.25193 -
Neurosurgery Jul 2019Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist,...
BACKGROUND
Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist, was previously completed in non-human primates.
OBJECTIVE
To investigate the safety and anti-epileptic effects of intracerebral muscimol infusion into the epileptic focus of patients with DRE.
METHODS
In this phase 1 clinical trial, 3 adult patients with DRE underwent CED into the seizure focus of artificial CSF vehicle followed by muscimol for 12 to 24 h each using a crossover design. Basic pathophysiology of the epileptic focus was examined by assessing the infusions' effects on seizure frequency, electroencephalogram (EEG) spike-wave activity, and power-spectral EEG frequency.
RESULTS
Inter-ictal neurological function remained normal in all patients. Pathological examination of resected specimens showed no infusion-related brain injuries. Seizure frequency decreased in 1 of 3 patients during muscimol infusion but was unchanged in all patients during vehicle infusion. Mean beta frequencies did not differ significantly before, during, or after infusion periods. Infused fluid provided insufficient MRI-signal to track infusate distribution. In the 2 yr after standard epilepsy surgery, 1 patient had temporary reduction in seizure frequency and 2 patients were seizure-free.
CONCLUSION
CED of muscimol into the epileptic focus of patients with DRE did not damage adjacent brain parenchyma or adversely affect seizure surgery outcome. This study did not confirm that intracerebral muscimol infusion effectively suppressed seizures. A surrogate tracer is recommended to track infusion distribution to the epileptic focus and surrounding structures in future studies using CED to suppress the seizure focus.
Topics: Adult; Anticonvulsants; Brain; Convection; Drug Resistant Epilepsy; Female; Humans; Infusions, Intraventricular; Magnetic Resonance Imaging; Male; Muscimol
PubMed: 30407567
DOI: 10.1093/neuros/nyy480 -
British Journal of Pharmacology Jul 19811 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres...
Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to gamma-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxin.
1 Interactions of depressant and anticonvulsant drugs with the neuronal gamma-aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.
Topics: Animals; Barbiturates; Benzodiazepines; Bicuculline; Dose-Response Relationship, Drug; Drug Interactions; Muscimol; Phenytoin; Picrotoxin; Rats; Receptors, Cell Surface; Receptors, GABA-A
PubMed: 6265019
DOI: 10.1111/j.1476-5381.1981.tb16810.x