GABA and Muscimol as Reversible Inactivation Tools in Learning and Memory

Majchrzak, Mark J.; Scala, Georges Di

doi:10.1155/np.2000.19

Cited by 53 publications

(33 citation statements)

References 74 publications

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“…As outlined in the Introduction, temporary regional brain inactivation may reveal some regional functions that have eluded lesion studies (Majchrzak and Di Scala 2000). Permanent brain lesions may fail to reveal normal behavioral contributions of the lesioned regions, because, following complete and permanent loss of hippocampal output, other brain regions may mediate these processes or because deficits could be masked by lesioninduced distal changes (cf.…”

Section: Discussionmentioning

confidence: 99%

“…We used microinfusion of the GABA A receptor agonist, muscimol (Majchrzak and Di Scala, 2000), to explore the effect of reversible neuronal inactivation of the ACgx on the encoding and retrieval/expression of recognition memory. In a series of four experiments, effects on encoding versus retrieval/expression were examined after both short (20 min) retention delays similar to those used in previous lesion studies and a longer (24 h) delay more similar to those used in the electrophysiological studies which have indicated a role for ACgx in NOR.…”

Section: United Kingdommentioning

confidence: 99%

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Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

et al. 2017

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Previous in vivo electrophysiological studies suggest that the anterior cingulate cortex (ACgx) is an important substrate of novel object recognition (NOR) memory. However, intervention studies are needed to confirm this conclusion and permanent lesion studies cannot distinguish effects on encoding and retrieval. The interval between encoding and retrieval tests may also be a critical determinant of the role of the ACgx. The current series of experiments used micro-infusion of the GABAA receptor agonist, muscimol, into ACgx to reversibly inactivate the area and distinguish its role in encoding and retrieval. ACgx infusions of muscimol, before encoding did not alter NOR assessed after a delay of 20 min or 24 h. However, when infused into the ACgx before retrieval muscimol impaired NOR assessed after a delay of 24 h, but not after a 20-min retention test. Together these findings suggest that the ACgx plays a time-dependent role in the retrieval, but not the encoding, of NOR memory, neuronal activation being required for the retrieval of remote (24 h old), but not recent (20 min old) visual memory.

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Section: Discussionmentioning

confidence: 99%

Section: United Kingdommentioning

confidence: 99%

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

et al. 2017

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“…Cells that are hyperpolarized by muscimol are less likely to fire action potentials and remain in that inactivated state until the drug is no longer effective (Majchrzak and Di Scala 2000). Muscimol binds with the GABA A receptor, which allows chloride ions to enter the cell, effectively decreasing neural activity beginning 30 min after infusion with the effect lasting at least 2 h post-infusion (Martin 1991).…”

Section: Muscimol Infusion Proceduresmentioning

confidence: 99%

Medial auditory thalamus is necessary for acquisition and retention of eyeblink conditioning to cochlear nucleus stimulation

2015

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Associative learning tasks commonly involve an auditory stimulus, which must be projected through the auditory system to the sites of memory induction for learning to occur. The cochlear nucleus (CN) projection to the pontine nuclei has been posited as the necessary auditory pathway for cerebellar learning, including eyeblink conditioning. However, the medial auditory thalamic nuclei (MATN), consisting of the medial division of the medial geniculate, suprageniculate, and posterior interlaminar nucleus have also been implicated as a critical auditory relay to the pontine nuclei for cerebellum-dependent motor learning. The MATN also conveys auditory information to the amygdala necessary for avoidance and fear conditioning. The current study used CN stimulation to increase activity in the pontine nuclei, relative to a tone stimulus, and possibly provide sufficient input to the cerebellum for acquisition or retention of eyeblink conditioning during MATN inactivation. Primary and secondary effects of CN stimulation and MATN inactivation were examined using 2-deoxyglucose autoradiography. Stimulation of CN increased activity in the pontine nuclei, however, this increase was not sufficient for cerebellar learning during MATN inactivation. Results of the current experiment provide additional evidence indicating the MATN may be the critical auditory relay for many associative learning tasks.Pavlovian eyeblink conditioning has been widely used to examine the behavioral and neural correlates of associative learning and memory (Gormezano et al. 1983;Christian and Thompson 2003;Freeman and Steinmetz 2011). This task is established by pairing a conditioned stimulus (CS), typically a tone, with an unconditioned stimulus (US), mild periorbital shock, that evokes an eyeblink reflex. After repeated CS -US presentations, an adaptive eyeblink conditioned response (CR) emerges prior to US onset. Converging lines of evidence indicate that the cerebellum, specifically the interpositus nucleus and cerebellar cortex, are essential sites of memory formation and storage for this task (McCormick et al.

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“…It is possible that the discrepancy between these earlier studies and the present data are due in part to differential effects of lesions and temporary inactivation. Although excitotoxic lesions preserve fibers of passage, cell bodies are extensively damaged (Zapeda et al, 2012), and it is likely that the surviving neurons which surround the damaged area function differently after the lesion (Majchrzak & Di Scala, 2000). Furthermore, several studies have indicated that functional recovery can occur following lesions in general (Casamenti et al, 1988;Gardiner et al, 1987;Wenk & Olton, 1984) and focal lesions of the hippocampus in particular (Zapeda et al, 2012).…”

Section: Histologymentioning

confidence: 99%

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

Cox

Czerniawski

Ree

et al. 2013

Neurobiology of Learning and Memory

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It is becoming increasingly clear that the time-dependent involvement of the hippocampus in the recall of acquired behaviors is more complicated than once thought.Several early studies demonstrated that hippocampal damage attenuates the expression of recent, but not remotely trained tasks. By contrast, an emerging body of evidence has shown that damage to, or inactivation of, the hippocampus impairs recall across a wide range of training-testing intervals. Collectively, these data suggest that the time course of hippocampal involvement in the storage or recall of previouslyacquired memories differs according to hippocampal subregion and the particular learning task under consideration. The present study examined the contributions of dorsal (DH) and ventral (VH) hippocampus to the expression of previously-acquired trace fear conditioning, a form of Pavlovian conditioning in which the presentation of an initially neutral cue or cues and a subsequent aversive stimulus is separated by a nostimulus (trace) interval. Specifically, either the GABA-A agonist muscimol or saline was ii infused into the DH or VH prior to testing 1, 7, 28, or 42 days after trace fear conditioning. The results revealed a marked dissociation: pre-testing inactivation of DH failed to impair performance at any time-point, while pre-testing inactivation of VH impaired performance at all time-points. Importantly, pre-testing inactivation of VH had no effect on the performance during testing of previously-acquired delay conditioning.Collectively, these data suggest that VH, but not DH, remains a neuroanatomical locus critical to the recall or expression of trace fear conditioning over an extended period of time.

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GABA and Muscimol as Reversible Inactivation Tools in Learning and Memory

Cited by 53 publications

References 74 publications

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

Role of the anterior cingulate cortex in the retrieval of novel object recognition memory after a long delay

Medial auditory thalamus is necessary for acquisition and retention of eyeblink conditioning to cochlear nucleus stimulation

Time course of dorsal and ventral hippocampal involvement in the expression of trace fear conditioning

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