Abad-Perez, P. | Search bioRxiv

bioRxiv2025

Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex

Cortical GABAergic interneurons (INs) expressing the neuropeptide vasoactive-intestinal peptide (VIP) predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting pyramidal cells (PCs) and facilitating cortical circuit plasticity. VIP INs are a molecularly heterogeneous group, but the physiological significance of this diversity is unclear at present. Here, we have characterized the functional diversity of VIP INs in the primary somatosensory cortex (vS1) using intersectional genetic approaches. We found that VIP INs are comprised of four primary populations that exhibit different laminar distributions, axonal and dendritic arbors, intrinsic electrophysiological properties, and efferent connectivity. Furthermore, we observe that these populations are differentially activated by long-range inputs, and display distinct responses to neuromodulation by endocannabinoids, acetylcholine and noradrenaline. Stimulation of VIP IN subpopulations in vivo results in differential effects on the cortical network, thus providing evidence for specialized modes of VIP IN-mediated regulation of PC activity during cortical information processing.

neuroscience↗

bioRxiv2021

NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE.

Abnormal NMDAr function has been linked to rhythmopathies, psychosis, and cognitive dysfunction in schizophrenia (SCZ). Here, we investigate the role of NMDAr hypofunction in pathological oscillations and behavior. We implanted mice with tetrodes in the dorsal hippocampus and medial prefrontal cortex (mPFC), administered the NMDAr antagonist MK801, and recorded oscillations during spontaneous exploration in an open field and in the y-maze spatial working memory test. Our results show that NMDAr blockade increased locomotor activity, impaired spatial working memory, and disrupted the correlation between oscillations and speed of movement, which is crucial for internal representations of distance. In the hippocampus, MK801 increased gamma oscillations and disrupted theta/gamma coupling. In the mPFC, MK801 increased the power of theta and gamma, generated high-frequency oscillations (HFO 155-185 Hz), and disrupted theta/gamma coupling. The performance of mice in the spatial working memory version of the y-maze was strongly correlated with CA1-PFC theta/ low gamma co-modulation. Thus, theta/gamma mediated by NMDAr function might be essential to explaining several of SCZs cognitive symptoms and might be crucial to explaining hippocampal-PFC interaction. Significance StatementNMDAr hypofunction might be the basis of cognitive symptoms and oscillopathies found in SCZ. In this work, we aimed to understand this link further. We found that NMDAr hypofunction altered theta/gamma co-modulation in the hippocampus and the PFC, explaining spatial working memory deficits.

neuroscience↗