For c, e Mann-Whitney U for comparisons to baseline Wilcoxon signed-rank for group comparisons. g, Hypothesized MD projections target prefrontal interneurons for independent control over amplification and suppression of cortical activity patterns. f, The two MD effects are uncorrelated ( n = 151 neurons). e, Population quantification of effect in d ( n = 373 neurons). d, Baseline spike rate suppression in another PL neuron after MD activation is unaffected by VIP + interneuron inactivation. c, Population quantification of effect in b ( n = 151 excitatory PL neurons). Bottom, this effect is eliminated by inactivation of local VIP + interneurons. b, Top, putative excitatory PL neuron showing amplification of its response to intracortical stimulation (blue tick) when the MD is activated. MDl, lateral MD MDc, central MD MDm, medial MD. Bottom right, somatic ChR2 in contralateral PL. Bottom middle, PL tetrode location (white arrow) eNHpR3.0-expressing VIP + neuron (inset). Bottom left, stabilized step function opsin (SSFO) MD expression. The specific subdivision of the PFC that we focus on in this study is the prelimbic cortex (PL).Ī, Top, cartoon of experimental set-up. We also hypothesized that suppression may be carried out by parvalbumin positive (PV +) prefrontal interneurons, as several studies have shown robust activation of these interneurons by the MD 12. As such, we hypothesized that the MD may contain two projections that differentially target prefrontal interneurons for independent control over input amplification and suppression (Fig. The two MD effects were uncorrelated, suggesting mechanistic independence (Fig. 1i, j), but, notably, did not affect basal cortical spike rates (Fig. Indeed, suppressing VIP + interneurons eliminated this MD effect (Fig. Therefore, we asked whether MD-dependent amplification of PFC functional connectivity ( Methods) was dependent on VIP + interneurons. We noted that, in contrast to sensory systems 9, the MD heavily targets cortical interneurons that are positive for vasoactive intestinal peptide (VIP +) 10 and known to be important for input amplification through disinhibition 11. 1), and confirmed that they were specific to this associative thalamocortical loop 8 (Extended Data Fig. To ask what the circuit mechanisms of these effects were, we first replicated them (Extended Data Fig. Activating the mediodorsal thalamus (MD) in mice has two distinct effects on neural activity in the prefrontal cortex (PFC): amplification of local functional connectivity 7 and suppression of spike rates 8.
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