Varela, Carmen

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 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.

Sparse thalamocortical cell population synchronicity during sleep spindle oscillations has been hypothesized to promote the integration of hippocampal memory information into associated neocortical representations 1. We asked the question of whether sparse or rhythmic activity in thalamocortical cells of the reuniens nucleus influence memory consolidation and cognitive flexibility during learning after sleep. For this study, I designed a novel attentional set-shifting task and incorporated optogenetics with closed-loop stimulation in sleeping rats to investigate the effects of sparse (nonrhythmic) or rhythmic spindle-like (~10Hz) activity in thalamic cells of the reuniens nucleus on learning and cognitive flexibility. We show that, as predicted, post-sleep setshifting performance improved after sleep with non-rhythmic optogenetic stimulation in the thalamic nucleus reuniens relative to rhythmic optogenetic stimulation. While both non-rhythmic and rhythmic optogenetic stimulation led to an increase in perseverative errors, only non-rhythmic optogenetic stimulation showed effects of learning from errors, which correlated with sleep, and which ultimately had a net benefit in set-shifting performance compared to rhythmic optogenetic stimulation and the control group.