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OPTOGENETICALLY DISRUPTING THE THALAMIC SPINDLE OSCILLATION DURING SLEEP IMPAIRS COGNITIVE FLEXIBILITY
Title
OPTOGENETICALLY DISRUPTING THE THALAMIC SPINDLE OSCILLATION DURING SLEEP IMPAIRS COGNITIVE FLEXIBILITY.
Creator
Yarden, Ori Simon, Varela, Carmen, Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science
Abstract/Description
A hypothesized model of spindle organization of thalamic and hippocampal spike dynamics (Figure 1) suggests that sparsity operates in spindles as an essential component of thalamic activity that could be contributing to flexibility in learning (Varela & Wilson, 2020). We asked the question of whether sparse spindle-like (10Hz non-rhythmic) or 10Hz rhythmic activity in thalamic cells of the reuniens nucleus influence cognitive flexibility during learning after sleep. By comparing the two...
Show moreA hypothesized model of spindle organization of thalamic and hippocampal spike dynamics (Figure 1) suggests that sparsity operates in spindles as an essential component of thalamic activity that could be contributing to flexibility in learning (Varela & Wilson, 2020). We asked the question of whether sparse spindle-like (10Hz non-rhythmic) or 10Hz rhythmic activity in thalamic cells of the reuniens nucleus influence cognitive flexibility during learning after sleep. By comparing the two stimulation protocols (“nonrhythmic” and “rhythmic”), we tested if disrupting the characteristic sparsity reveals any changes in flexibility during learning after sleep. Results showed that sleep accompanied 10Hz rhythmic optogenetic stimulation of thalamic nucleus reuniens impaired rule-switching (or set-shifting) performance and disrupted the sleep enhancing rule-switch associated increase in vicarious trial and error (VTE), which we used as a metric for deliberation. We found that rule-switching was associated with a subsequent increase in VTE, as were incorrect choices, and when rats subsequently made correct choices. Instead, stimulating against the endogenous thalamocortical spindle oscillation (i.e. sleep accompanied 10Hz rhythmic optogenetic stimulation) resulted in a significant disruption in post-sleep performance and VTE during, but not prior to, rule-switching. Lastly, optogenetic 10Hz stimulation of the thalamic nucleus reuniens did not affect sleeping or waking behavior during the sleep box session but it did show a clear though nonsignificant increase in waking head velocities; thus, changes in cognitive flexibility and VTE cannot be explained by any changes in sleep itself, but rather due to the after-effects the specific patterns of 10Hz optogenetic stimulation in thalamic nucleus reuniens applied during sleep had on cognition.
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Date Issued
2023
PURL
http://purl.flvc.org/fau/fd/FA00014275
Subject Headings
Optogenetics, Midline Thalamic Nuclei, Sleep
Format
Document (PDF)
Behavioral and Electrophysiological Properties of Nucleus Reuniens: Role in Arousal, Spatial Navigation and Cognitive Processes
Title
Behavioral and Electrophysiological Properties of Nucleus Reuniens: Role in Arousal, Spatial Navigation and Cognitive Processes.
Creator
Viena, Tatiana Danela, Vertes, Robert P., Florida Atlantic University, Charles E. Schmidt College of Science, Center for Complex Systems and Brain Sciences
Abstract/Description
The hippocampal-medial prefrontal circuit has been shown to serve a critical role in decision making and goal directed actions. While the hippocampus (HF) exerts a direct influence on the medial prefrontal cortex (mPFC), there are no direct return projections from the mPFC to the HF. The nucleus reuniens (RE) of the midline thalamus is strongly reciprocally connected with the HF and mPFC and represents the major link between these structures. We investigated the role of RE in functions...
Show moreThe hippocampal-medial prefrontal circuit has been shown to serve a critical role in decision making and goal directed actions. While the hippocampus (HF) exerts a direct influence on the medial prefrontal cortex (mPFC), there are no direct return projections from the mPFC to the HF. The nucleus reuniens (RE) of the midline thalamus is strongly reciprocally connected with the HF and mPFC and represents the major link between these structures. We investigated the role of RE in functions associated with the hippocampus and the mPFC -- or their interactions. Using two different inactivation techniques (pharmacological and chemogenetic), we sought to further define the role of RE in spatial working memory (SWM) and behavioral flexibility using a modified delayed non-match to sample (DNMS) working memory task. We found that the reversible inactivation of RE with muscimol critically impaired SWM performance, abolished well-established spatial strategies and produced a profound inability to correct non-rewarded, incorrect choices on the T-maze (perseverative responding). We observed similar impairments in SWM following the chemogenetic (DREADDs) inactivation of RE or selective RE projections to the ventral HF. In addition, we showed that the inhibition of RE terminals to the dorsal or ventral HF altered task related behaviors by increasing or decreasing the time to initiate the task or reach the reward, respectively. Finally, we examined discharge properties of RE cells across sleep-wake states in behaving rats. We found that the majority of RE cells discharge at high rates of activity in waking and REM and at significantly reduced rates in SWS, with a subpopulation firing rhythmically in bursts during SWS. We identified five distinct subtypes of RE cells that discharged differently across vigilant states; those firing at highest rates in waking (W1, W2), in REM sleep (R1, R2) and SWS (S1). Given the differential patterns of activity of these cells, we proposed they may serve distinct functions in waking – and possibly in SWS/REM sleep. In sum, our findings indicate that RE is critically involved in mnemonic and executive functions and the heterogeneous activity of these cells support a role for RE in arousal/attention, spatial working memory and cognition.
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Date Issued
2018
PURL
http://purl.flvc.org/fau/fd/FA00013139
Subject Headings
Midline Thalamic Nuclei, Hippocampus, Prefrontal cortex, Neural pathways, Arousal (Physiology), Space Perception, Cognition
Format
Document (PDF)