Development-Dependent Plasticity in Vasoactive Intestinal Polypeptide Neurons in the Infralimbic Cortex

Abstract

The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared to female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.

Function and development of interneurons involved in brain tissue oxygen regulation

“…The interference with normal maturation processes early in development may affect NOS interneuron neurovascular interactions to a greater degree, while insults later in development may be more targeted toward VIP- and SST-mediated mechanisms of oxygen regulation. Importantly, these differences in development also point to age-related pathological onset of various psychiatric disorders, such as schizophrenia and anxiety disorders ( Kim-Cohen et al, 2003 ; Dalsgaard et al, 2020 ; Collins and Ninan, 2021 ), as well as the development of learning deficits following neonatal anesthesia exposure ( Gascoigne et al, 2021 , 2022 ). Research in this field is ongoing and will likely be able to address interneuron subtype specific contributions to a range of pathologies.…”

“…A recent study has been able to contrast the development of VIP and SST interneurons in a mouse model (Collins and Ninan, 2021). The investigators reported VIP interneurons in the adolescent brain exhibits enhanced input signaling with diminished membrane excitability.…”

“…Type I cells exhibit more intense immunohistochemical markers of NOS characteristics and are distributed throughout cortical layers, while type II are typically found in the supragranular in humans ( Duchemin et al, 2012 ). It is interesting that VIP interneurons are very sensitive to temperature changes, so that increases in the temperature decrease the probability of action potentials ( Collins and Ninan, 2021 ). Perhaps this property is related to local hemodynamic regulation, such that, when experiencing relatively high temperature, VIP neurons do not exacerbate the vasodilatory consequences of the heat itself.…”

“…As described previously, VIP and SST interneurons functionally interact with one another, and their developmental trajectories are similarly interconnected. A recent study has been able to contrast the development of VIP and SST interneurons in a mouse model ( Collins and Ninan, 2021 ). The investigators reported VIP interneurons in the adolescent brain exhibits enhanced input signaling with diminished membrane excitability.…”

“…In this study, in the adolescent stage of development (postnatal day 14 in mice) VIP interneurons demonstrated greater selectivity to input signals, with diminished overall response rates, while SST interneurons showed increased excitability from more general sensory stimulation ( Kastli et al, 2020 ). The combination of decreased VIP and increased SST inhibitory signaling seems to lower the disinhibition of pyramidal cells and, in turn, affect their ability to undergo plasticity ( Collins and Ninan, 2021 ). Thus, VIP and SST undergo a dramatic divergence in development, which should be reflected in the changes of neurovascular and brain tissue oxygen regulations.…”