Reciprocal Circuits Linking the Prefrontal Cortex with Dorsal and Ventral Thalamic Nuclei

Abstract

Reciprocal interactions between the prefrontal cortex (PFC) and thalamus play a critical role in cognition, but the underlying circuits remain poorly understood. Here we use optogenetics to dissect the specificity and dynamics of cortico-thalamo-cortical networks in the mouse brain. We find that cortico-thalamic (CT) neurons in prelimbic PFC project to both mediodorsal (MD) and ventromedial (VM) thalamus, where layer 5 and 6 inputs activate thalamo-cortical (TC) neurons with distinct temporal profiles. We show that TC neurons in MD and VM in turn make distinct connections in PFC, with MD preferentially and strongly activating layer 2/3 cortico-cortical (CC) neurons. Finally, we assess local connections from superficial CC to deep CT neurons, which link thalamo-cortical and cortico-thalamic networks within the PFC. Together our findings indicate that PFC strongly drives neurons in the thalamus, whereas MD and VM indirectly influence reciprocally connected neurons in the PFC, providing a mechanistic understanding of these circuits.

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

“…Outputs from MD to prefrontal cortex, primarily innervate the dendrites of prefrontal pyramidal neurons located in layer 3, with fewer contacts in layers 5 and 6 (Kuroda et al ., ; Delevich et al ., ). Recent evidence also indicates that MD contacts cortico‐cortical neurons in layer 2/3 (Collins et al ., ). Moreover, sparse MD projection to layer 1 has been observed together with those of intralaminar nuclei (Kuroda et al ., ; Collins et al ., ).…”

“…Recent evidence also indicates that MD contacts cortico‐cortical neurons in layer 2/3 (Collins et al ., ). Moreover, sparse MD projection to layer 1 has been observed together with those of intralaminar nuclei (Kuroda et al ., ; Collins et al ., ).…”

“…Recently, Collins et al (2018) using optogenetic stimulation of prefrontal corticothalamic neurons of layer 6 and some of layer 5, evoked monosynaptic excitatory potentials, with similar synaptic properties, in MD and VM. Moreover, colocalization of thalamic retrograde markers from MD and VM in corticothalamic neurons is observed with bifurcated axons contacting both MD and VM.…”

Mediodorsal and ventromedial thalamus engage distinct L1 circuits in the prefrontal cortex

“…The PFC engages several higher-order nuclei, including reciprocal interactions with mediodorsal (MD) and ventromedial (VM) thalamus (Collins et al, 2018;Gabbott et al, 2005). Connections with MD sustain delay period activity during working memory (Bolkan et al, 2017;Schmitt et al, 2017), whereas those with VM regulate arousal (Honjoh et al, 2018).…”

“…Connections with MD sustain delay period activity during working memory (Bolkan et al, 2017;Schmitt et al, 2017), whereas those with VM regulate arousal (Honjoh et al, 2018). The behavioral roles of these nuclei likely reflect their impact on different circuits within the PFC, with MD inputs driving layer 2/3 (L2/3) pyramidal cells, and VM contacting but not firing L2/3 and L5 pyramidal cells (Collins et al, 2018). Interestingly, both MD and VM inputs also project to L1, but it remains unclear how connections in superficial layers contribute to their functional influence on the PFC.…”