Local Injection Of Muscimol Research Articles

Primate Amygdalo-Nigral Pathway for Boosting Oculomotor Action in Motivating Situations.

SummaryA primary function of the primate amygdala is to modulate behavior based on emotional cues. To study the underlying neural mechanism, we first inactivated the amygdala locally and temporarily by injecting a GABA agonist. Then, saccadic eye movements and gaze were suppressed only on the contralateral side. Next, we performed optogenetic activation after injecting a viral vector into the amygdala. Optical stimulation in the amygdala excited amygdala neurons, whereas optical stimulation of axon terminals in the substantia nigra pars reticulata inhibited nigra neurons. Optical stimulation in either structure facilitated saccades to the contralateral side. These data suggest that the amygdala controls saccades and gaze through the basal ganglia output to the superior colliculus. Importantly, this amygdala-derived circuit mediates emotional context information, whereas the internal basal ganglia circuit mediates object value information. This finding demonstrates a basic mechanism whereby basal ganglia output can be modulated by other areas conveying distinct information.

The activity of thalamic nucleus reuniens is critical for memory retrieval, but not essential for the early phase of "off-line" consolidation.

Spatial navigation depends on the hippocampal function, but also requires bidirectional interactions between the hippocampus (HPC) and the prefrontal cortex (PFC). The cross-regional communication is typically regulated by critical nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is reciprocally connected to both HPC and PFC and may coordinate the information flow within the HPC–PFC pathway. Here we examined if RE activity contributes to the spatial memory consolidation. Rats were trained to find reward following a complex trajectory on a crossword-like maze. Immediately after each of the five daily learning sessions the RE was reversibly inactivated by local injection of muscimol. The post-training RE inactivation affected neither the spatial task acquisition nor the memory retention, which was tested after a 20-d “forgetting” period. In contrast, the RE inactivation in well-trained rats prior to the maze exposure impaired the task performance without affecting locomotion or appetitive motivation. Our results support the role of the RE in memory retrieval and/or “online” processing of spatial information, but do not provide evidence for its engagement in “off-line” processing, at least within a time window immediately following learning experience.

Two subdivisions of macaque LIP process visual-oculomotor information differently

Although the cerebral cortex is thought to be composed of functionally distinct areas, the actual parcellation of area and assignment of function are still highly controversial. An example is the much-studied lateral intraparietal cortex (LIP). Despite the general agreement that LIP plays an important role in visual-oculomotor transformation, it remains unclear whether the area is primary sensory- or motor-related (the attention-intention debate). Although LIP has been considered as a functionally unitary area, its dorsal (LIPd) and ventral (LIPv) parts differ in local morphology and long-distance connectivity. In particular, LIPv has much stronger connections with two oculomotor centers, the frontal eye field and the deep layers of the superior colliculus, than does LIPd. Such anatomical distinctions imply that compared with LIPd, LIPv might be more involved in oculomotor processing. We tested this hypothesis physiologically with a memory saccade task and a gap saccade task. We found that LIP neurons with persistent memory activities in memory saccade are primarily provoked either by visual stimulation (vision-related) or by both visual and saccadic events (vision-saccade-related) in gap saccade. The distribution changes from predominantly vision-related to predominantly vision-saccade-related as the recording depth increases along the dorsal-ventral dimension. Consistently, the simultaneously recorded local field potential also changes from visual evoked to saccade evoked. Finally, local injection of muscimol (GABA agonist) in LIPv, but not in LIPd, dramatically decreases the proportion of express saccades. With these results, we conclude that LIPd and LIPv are more involved in visual and visual-saccadic processing, respectively.

Involvement of the lateral prefrontal cortex in conditional suppression of gaze shift

Conditional execution and suppression of gaze shift are important in everyday life. To examine the possible involvement of the lateral prefrontal cortex (LPFC) in this process, we induced a local and reversible inactivation by injecting muscimol into 66 sites within the LPFC of monkeys and examined muscimol's effect on their performance in an oculomotor Go/No-Go task. This task required a subject to execute (Go) or suppress (No-Go) its gaze toward a target location in response to an instructional visual cue. Local injection of muscimol into 22 regions of the LPFC resulted in significant increases in the number of error saccades toward a few specific target locations during No-Go trials, whereas there were no error saccades in the Go trials. The onset latency of error saccades in No-Go trials was significantly longer than that of correct saccades in Go trials, but their velocity and amplitude were similar to those of correct saccades in Go trials. Go correct saccades appeared intact after the injections. These findings provide evidence that different regions of the LPFC are involved in the conditional suppression of gaze shift toward a few specific target locations, which may occur through a top-down suppressive mechanism.

Lipopolysaccharide Increases γ‐Aminobutyric Acid Synthesis in Medial Preoptic Neurones in Association with Inhibition of Steroid‐Induced Luteinising Hormone Surge in Female Rats

Lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, inhibits gonadotrophin secretion and ovulation in female mammals. The present study was undertaken to examine whether gamma-aminobutyric acid (GABA)-synthesising neurones in the medial preoptic area (mPOA) may be involved in the inhibition by LPS of progesterone-induced luteinising hormone (LH) surge in ovariectomised oestrogen-primed rats. An intravenous injection of LPS (10 microg) at noon significantly increased the content of glutamic acid decarboxylase 67 (GAD67), a GABA-synthesising enzyme, in brain tissues including the mPOA. LPS treatment also significantly increased the number of detectable GAD67-immunoreactive (ir) as well as GABA-ir cells in the mPOA, compared to control rats. The same LPS challenge completely eliminated the steroid-induced LH surge, which was normally induced in control rats in the afternoon. A local injection of muscimol (100 ng), a GABA(A) receptor agonist, into the mPOA also significantly attenuated the LH surge, mimicking the effect of LPS. These results suggest that LPS stimulates GABA synthesis in preoptic neurones, which in turn inhibit the LH surge in female rats. The results also support the hypothesis that diminution of the GABAergic suppressive activity in the mPOA permits the LH surge to be induced.

Involvement of the dorsolateral prefrontal cortex of monkeys in visuospatial target selection.

To examine the involvement of the dorsolateral prefrontal cortex (PFC) in visuospatial target selection, we induced local, reversible inactivation with muscimol at various sites in the dorsolateral PFC of two rhesus monkeys while they performed oculomotor visual search (OVS) and oculomotor detection (OD) tasks. The OVS task required the subject to select a target stimulus from among distractors and to make a saccade to the target location (target selection was required for correct performance), whereas the OD task only required a saccade to the target (target selection was not required for correct performance). The local injection of muscimol (5 microg, 1 microl) into the dorsolateral PFC induced a specific deficit in the OVS task but not in the OD task. The deficit in the OVS task was characterized by the disordering of saccades for some (mostly a few) particular target locations as well as by prolongation of the time required for the visual search in most cases. The target locations affected by muscimol were biased to the contralateral visual field. Further, the OVS task with "pop-out" and "non-pop-out" conditions was similarly impaired by muscimol injection. These results suggest that the dorsolateral PFC plays a role in target selection in visual space to guide goal-directed motor acts and particular sites are involved in target selection for a particular visuospatial coordinate. Further, this function of the dorsolateral PFC appears to involve both top-down (active) and bottom-up (passive) target-selection/selective attention processes to control interfering information (distractors).

Role of the rostral superior colliculus in active visual fixation and execution of express saccades.

1. In the rostral pole of the monkey superior colliculus (SC) a subset of neurons (fixation cells) discharge tonically when a monkey actively fixates a target spot and pause during the execution of saccadic eye movements. 2. To test whether these fixation cells are necessary for the control of visual fixation and saccade suppression, we artificially inhibited them with a local injection of muscimol, an agonist of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). After injection of muscimol into the rostral pole of one SC, the monkey was less able to suppress the initiation of saccades. Many unwanted visually guided saccades were initiated less than 100 ms after onset of a peripheral visual stimulus and therefore fell into the range of express saccades. 3. We propose that fixation cells in the rostral SC form part of a fixation system that facilitates active visual fixation and suppresses the initiation of unwanted saccadic eye movements. Express saccades can only occur when activity in this fixation system is reduced.

GABAergic mechanisms mediating rotational behavior in rats: Differences between dorsal and ventral striatum

Local injection of muscimol into the dorsal or ventral striatum of rats did not induce any rotational activity, but injection of picrotoxin into ventral striatal aspects induced an intense contralateral rotation. Amphetamine pretreatment resulted in an ipsilateral rotation after muscimol injection into dorsal striatum and in a complex rotational pattern after ventral injection, characterized by an initial short-lasting ipsilateral rotation followed by a long-lasting contralateral rotation. The contralateral rotation induced by picrotoxin was abolished by amphetamine pretreatment. These results indicate a functional heterogeneity between dorsal and ventral striatal mechanisms mediating rotational behavior, and a different pattern of dopamine-GABA interactions between dorsal and ventral striatum.

Comparison of deficits induced by a local injection of muscimol into the first somatosensory cortex (SI) or motor cortex on the fine hand movements of a trained monkey

Comparison of deficits induced by a local injection of muscimol into the first somatosensory cortex (SI) or motor cortex on the fine hand movements of a trained monkey

Neuroanatomical site of the inhibitory influence of anxiolytic drugs on central serotonergic transmission

The neuroanatomical site of the inhibitory influence of anxiolytics on central serotonergic transmission has been investigated in the rat by studying the effect of systematic or intracerebral administration of these drugs on cerebral serotonin (5-HT) synthesis. Systematic administration of diazepam (3 mg/kg s.c.) or flunitrazepam (1 mg/kg, s.c.) caused a reduction of 5-HT synthesis (as measured by the accumulation of 5-hydroxytryptophan after inhibition of aromatic amino acid decar☐ylase) in the hippocampus but not in the cerebral cortex, striatum, cerebellum or spinal cord of the rat. Zopiclone (22 mg/kg, s.c.) decreased the amine synthesis in hippocampus, striatum and prefrontal cortex. The decrease of hippocampal 5-HT synthesis induced by diazepam (5 mg/kg, s.c.) was antagonized by the benzodiazepine antagonist Ro 15-1788 (2 × 30 mg/kg, s.c.) but not by bicuculline (2 × 1 mg/kg, s.c.). Acute cerebral hemitransection or electrolytic lesion of the fasciculus retroflexus did not prevent the ability of diazepam (5 mg/kg, i.p.) to diminish hippocampal 5-HT synthesis. Local infusion of diazepam (15 μg) or flurazepam (1.5 μg) into the hippocampus of conscious rats (via indwelling cannulae) markedly reduced 5-HT synthesis in this brain area whereas infusion of these drugs into the raphémedianus (origin of the serotonergic afferents to the hippocampus) failed to affect hippocampal 5-HT synthesis. In contrast, local injection of muscimol (25–150 ng) into the raphémedianus reduced 5-HT synthesis in the hippocampus. This effect of muscimol was potentiated by a systematic administration of diazepam or an intra-raphémedianus infusion of flurazepam (at doses or concentrations which exhibited no intrinsic activity). It is concluded from these data that anxiolytic drugs exert an inhibitory influence on hippocampal serotonergic neurons which is mediated primarily via GABA-independent benzodiazepine receptors located in the vicinity of serotonergic nerve terminals.

Further evidence for, and nature of, the facilitatory GABAergic influence on central noradrenergic transmission.

In order to explore the nature of the facilitatory GABAergic control of cerebral noradrenergic neurons, we have studied the effect of a variety of GABA mimetics (given systemically or injected locally into brain areas containing noradrenergic cell bodies or terminals) on several indices of noradrenaline turnover in the rat brain. Systemic administration of both direct and indirect acting GABA mimetics enhanced; 1) the pargyline induced accumulation of normetanephrine in the hypothalamus; 2) total DOPEG levels in a number of brain regions innervated by noradrenergic neurons; 3) both DOPAC and MOPEG levels in noradrenergic cell body areas (A1, A2 and A6). These effects are probably mediated by GABAA receptors as specific GABAA or mixed GABAA/GABAB agonists but not the GABAB agonist baclofen enhanced noradrenaline turnover. Interruption of noradrenergic impulse flow (by local injection of tetrodotoxin or by hemitransection) blocked the ability of progabide to increase DOPEG concentrations in the hypothalamus and cerebral cortex. Similarly, the co-administration of clonidine with progabide antagonized the progabide-induced increase in hypothalamic total DOPEG levels. Co-administration of yohimbine with progabide provoked an additive effect on hypothalamic DOPEG levels at moderate but not at high doses of yohimbine. Thus, the acceleration of noradrenaline turnover induced by GABA mimetics appears to depend on ongoing activity in noradrenergic neurons and occurs via an increase in neuronal discharges. Local injection of muscimol into the nucleus accumbens or hypothalamus failed to affect DOPEG levels in these structures; similarly, local injection of muscimol into the locus coeruleus failed to modify DOPEG levels in corresponding noradrenergic projection areas. These data indicate that the GABAergic influence is not exerted via GABA receptors located on noradrenergic cell bodies or nerve endings. Furthermore, since systemically administered progabide still increased hypothalamic DOPEG levels after ibotenate-induced destruction of the hypothalamic neuronal cell bodies, a presynaptic modulation of noradrenergic neurons by local GABAergic interneurons is excluded. Chemical destruction of serotoninergic pathways or enhancement of 5-HT transmission by quipazine failed to alter the ability of progabide to increase cerebral DOPEG levels. Moreover, scopolamine or naloxone also failed to affect the progabide-induced increase in cerebral DOPEG levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential deficits in manipulative behaviors induced by local injection of muscimol in different areas of the hand region of consicous monkey somatosensory cortex (SI)

Differential deficits in manipulative behaviors induced by local injection of muscimol in different areas of the hand region of consicous monkey somatosensory cortex (SI)

Differential deficits in manipulative behaviors induced by local injection of muscimol in different areas of the hand region of consicous monkey somatosensory cortex (SI)

Arm displacements applied to the passive, but awake monkey are powerful stimuli for activating neurones in somatotopically appropriate areas of the precentral cortex. We have found that neurones in medial area 6 (SMA) and in lateral area 6 (PMC) may likewise be activated by such kinesthetic stimuli, at latencies which are only slightly longer than in area 4. Confirming previous findings, PMC neurones were sometimes also responsive to visual stimuli. The ‘somatosensory’ cells in the SMA were found in the microexcitable zone of the more posterior part of the SMA from where motor effects were elicited in arm and trunk muscles. These sensory neurones tended to be clustered together and they were only exceptionally excited antidromically by peduncular stimulation. Thus, somatosensory signals have access to both the PMC and the SMA suggesting that both areas may be implicated in sensory-guided or sensory-triggered movements.

Transient seizure activity induced by acetylcarnitine

Intracerebral injection of L-acetylcarnitine in rats induced interictal and ictal epileptic phenomena with immediate onset, lasting up to 4 h. Pretreatment with systemic atropine prevents all epileptiform phenomena. Local injection of muscimol and THIP abolish ictal events, but not single spikes. L-carnitine induced only ictal discharges with a latency of 40–90 min. Acetylcarnitine epileptogenic properties are probably related to muscarinic agonism. The transition from interictal to ictal events may involve failure of GABAergic mechanisms.