Thalamic circuits for independent control of prefrontal signal and noise

Abstract

Interactions between the mediodorsal thalamus and the prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision-making1, but the precise mechanisms are unknown. Here we identify two distinct mediodorsal projections to the prefrontal cortex that have complementary mechanistic roles in decision-making under uncertainty. Specifically, we found that a dopamine receptor (D2)-expressing projection amplifies prefrontal signals when task inputs are sparse and a kainate receptor (GRIK4) expressing-projection suppresses prefrontal noise when task inputs are dense but conflicting. Collectively, our data suggest that there are distinct brain mechanisms for handling uncertainty due to low signals versus uncertainty due to high noise, and provide a mechanistic entry point for correcting decision-making abnormalities in disorders that have a prominent prefrontal component2–6.

Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson’s disease

“…Interactions between thalamus and prefrontal cortex are important in dealing with perceptual uncertainty during decision making 82 . Two separate pathways may exist for this, with low-signal-related uncertainty (as would be expected with reduced bottom-up sensory input) resolved by dopaminergic projections from medial thalamus that increase prefrontal output 83 .…”

“…Interactions between thalamus and prefrontal cortex are important in dealing with perceptual uncertainty during decision making 82 . Two separate pathways may exist for this, with low-signal-related uncertainty (as would be expected with reduced bottom-up sensory input) resolved by dopaminergic projections from medial thalamus that increase prefrontal output 83 . Interestingly, changes in thalamic resting state functional connectivity 84 , as well as changes in thalamocortical effective connectivity 85 may also underlie hallucinations during exposure to LSD, consistent with a more general role for changes in thalamic connectivity in hallucinations in other contexts 86 .…”

A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome

“…Work in mice has shown that thalamocortical projections are critical for encoding cognitive functions that are affected in schizophrenia. For instance, reciprocal activity between the mediodorsal nucleus of the thalamus and the prefrontal cortex is required for maintenance of spatial working memory, cognitive flexibility, adaptive decision making, and sustaining attentional control in rodents ( Bolkan et al, 2017 ; Schmitt et al, 2017 ; Alcaraz et al, 2018 ; Rikhye et al, 2018a ; Mukherjee et al, 2021 ). However, the role of these thalamocortical circuits in cognitive symptoms has yet to be established in mouse models of 22q11DS or other schizophrenia-associated CNVs.…”

Synthetic Spatial Foraging With Active Inference in a Geocaching Task

“…The role of uncertainty in cognition has been investigated under different assumptions and frameworks ( Grupe and Nitschke, 2013 ; Hasson, 2017 ; Peters et al, 2017 ; Mukherjee et al, 2021 ; Walker et al, 2021 ). In learning processes, uncertainty has a direct relationship with statistical and parametric learning, in that the latter aims to find patterns of consistent associations over separate experiences, while the modulation of the former directly affects the latter via predictive processes ( Hasson, 2017 ).…”