Adolescent Thalamocortical Inhibition Alters Prefrontal Excitation-Inhibition Balance.

Autor:	Petersen D; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032., Raudales R; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032., Silva AK; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032., Kellendonk C; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.; Department of Molecular Pharmacology & Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032., Canetta S; Department of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA.; Division of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, 10032.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 20. Date of Electronic Publication: 2024 Mar 20.
DOI:	10.1101/2023.11.22.568048
Abstrakt:	Adolescent inhibition of thalamo-cortical projections from postnatal day P20-50 leads to long lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuit connectivity during adolescence. Here, we used chemogenetic tools to inhibit thalamo-prefrontal projections in the mouse from P20-35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target twenty-four hours later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III nucleus accumbens (NAc) and layer V/VI medio-dorsal thalamus projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only changed in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosally-projecting neurons. Increased inhibition of intra-prefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition (P20-P35). Competing Interests: Conflict of Interest Statement: The authors declare no competing financial interests.
Databáze:	MEDLINE
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