Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

Abstract

The thalamus engages in sensation, action, and cognition, but the structure underlying these functions is poorly understood. Thalamic innervation of associative cortex targets several interneuron types, modulating dynamics and influencing plasticity. Is this structure-function relationship distinct from that of sensory thalamocortical systems? Here, we systematically compared function and structure across a sensory and an associative thalamocortical loop in the mouse. Enhancing excitability of mediodorsal thalamus, an associative structure, resulted in prefrontal activity dominated by inhibition. Equivalent enhancement of medial geniculate excitability robustly drove auditory cortical excitation. Structurally, geniculate axons innervated excitatory cortical targets in a preferential manner and with larger synaptic terminals, providing a putative explanation for functional divergence. The two thalamic circuits also had distinct input patterns, with mediodorsal thalamus receiving innervation from a diverse set of cortical areas. Altogether, our findings contribute to the emerging view of functional diversity across thalamic microcircuits and its structural basis.

Optical mini-stroke of thalamic networks impairs sleep stability, topography and cognition

“…Interestingly, in humans other brain disorderscharacterized by strong deficits in cognition -have been often associated with altered PFC excitation including spindles density and changes in the structure and/or activity of the medial thalamus (19,(94)(95)(96). These investigations are further supported by the high density of medial thalamic projections to frontal cortical regions, while other thalamic nuclei preferentially regulate activity of more parietal cortices (18,22,25,26,61,97). Here, we found a negative correlation between frontal spindles density and working memory performance that highlight the circuit specificity of our Opto-STROKE model and further supports the notion that these two phenomena might be functionally related and dependent on IL-PFC projections integrity (Figure 5M).…”

“…Interestingly, we found that stroke lesions in the IL induced significant changes in the thalamocortical connectivity, and, in particular, in the IL-to-ACC and -PL circuits including synaptic contacts onto parvalbumin-expressing cells (Figure 1G, H, I, J). It is possible that some of IL projections contact other cell types in these areas, however, previous reports have shown that the majority of them project towards inhibitory interneurons (18,26). Determining the exact contribution of IL-stroke to the changes in local cortical connectivity awaits further investigation.…”

“…According to their broad system of efferent and afferent projections, the IL have been recognized as higher order thalamic nuclei, involved in higher associative cognitive functions. Previous works have shown that MD and CMT neurons extensively project to parvalbumin expressing interneurons (PV+) in the anterior cingulate cortex (ACC) (17)(18)(19)(20) , which are responsible for feedforward inhibition ultimately modulating cortical excitability and brain states (21)(22)(23). Moreover, IL -prefrontal cortex (PFC) circuits have been shown to play a role in memory and attention-related tasks (24)(25)(26).…”

Corticothalamic Pathways From Layer 5: Emerging Roles in Computation and Pathology

“…Given this evidence for HO TC induction of sustained depolarizations, HO thalamus could play a role in coordinating such transient ensembles of “prepared” neurons and sensitizing the cortex to additional synaptic inputs. One experimental difficulty in assessing HO TC’s impact in vivo that mass optogenetic excitation and inhibition does not lend itself to physiological stimulation patterns and it is likely that more naturalistic interventions will reveal nuances of the effect of HO TC projections–for example, the use of step-opsins by Mukherjee et al (2020) to show that enhancement of MD thalamus led to inhibition dominating activity in PFC.…”

Stable thalamocortical learning between medial-dorsal thalamus and cortical attractor networks captures cognitive flexibility

“…The explanation starts from the debate about whether thalamus is merely a relay hub, or it is actually doing computation based on the signal from prefrontal cortex. A recent paper [14] compared the pathway of the medial geniculate body to A1 neurons and the pathway from MD to prelimbic prefrontal cortex, and this comparison shows distinctive functions in different areas of the thalamus. The former pathway is a sensory thalamic pathway, which affects the A1 circuit mainly through excitatory neurons, so it is just a first order thalamic nucleus.…”