Thalamic projections sustain prefrontal activity during working memory maintenance.

Area of Science:

• Neuroscience
• Cognitive Neuroscience
• Systems Neuroscience

Background:

• The mediodorsal thalamus (MD) and prefrontal cortex (PFC) have reciprocal connections, crucial for cognitive functions.
• Reduced MD-PFC connectivity is linked to cognitive deficits, like working memory impairments, in schizophrenia.
• The precise mechanistic role of thalamo-prefrontal circuits in working memory remains unclear.

Purpose of the Study:

• To elucidate the directional circuit interactions between the MD and medial PFC (mPFC) in supporting working memory.
• To identify specific neuronal populations in the mPFC involved in working memory maintenance and choice selection.
• To investigate the influence of MD inputs on mPFC neuronal activity during working memory tasks.

Main Methods:

• Utilized pathway-specific inhibition techniques in mice to dissect the functional roles of MD-mPFC connections.
• Recorded neuronal activity in the mPFC during a working memory task to identify delay-tuned and spatially tuned neurons.
• Manipulated MD excitability to assess its causal impact on task performance.

Main Results:

• MD-to-mPFC pathways are critical for working memory maintenance, while mPFC-to-MD pathways support subsequent choice.
• Identified mPFC neurons with elevated spiking during delay periods, dependent on MD inputs for sustained activity.
• Demonstrated that delay-tuned and spatially tuned mPFC neurons rely differentially and exclusively on MD and hippocampal inputs, respectively.
• Found that enhancing MD excitability significantly improved working memory task performance.

Conclusions:

• The MD plays a vital role in sustaining prefrontal neuronal activity essential for working memory maintenance.
• MD-PFC circuit dynamics are mechanistically linked to working memory function and may represent a therapeutic target for cognitive impairments.