Biology subjects

Harris, A. Z.

Publications and source records attributed to Harris, A. Z..

2 recordsLinked to original sources

bioRxiv2021

Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, we demonstrate that inhibition of prefrontal parvalbumin-expressing interneurons during the juvenile and adolescent period, results in persistent impairments in adult prefrontal circuit connectivity, in vivo network function and behavioral flexibility that can be reversed by targeted activation of parvalbumin interneurons in adulthood. In contrast, transient suppression of parvalbumin interneuron activity in adulthood produces no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal circuit maturation and highlight how abnormal parvalbumin interneuron activity during development alters adult prefrontal circuit function and cognitive behavior.

neuroscience↗

bioRxiv2020

Ventral tegmental area GABA neurons mediate stress-induced anhedonia.

Stressful experiences frequently precede depressive episodes1. Depression results in anhedonia, or disrupted reward-seeking, in most patients2. In humans3,4 and rodents5,6, stress can disrupt reward-seeking, providing a potential mechanism by which stress can precipitate depression7-9. Yet despite decades investigating how stress modulates dopamine neuron transmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc), the underpinnings of the stress-anhedonia transition remain elusive10-13. Here we show that during restraint stress, VTA GABA neurons drive low frequency NAc LFP oscillations, rhythmically modulating NAc firing rates. The strength of these stress-induced NAc oscillations predict the degree of impaired reward-seeking upon release from restraint. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and reverses the effect of stress on reward-seeking. By contrast, mimicking these oscillations with rhythmic VTA GABA stimulation in the absence of stress blunts subsequent reward-seeking. These experiments demonstrate that VTA GABA inputs to the NAc are both necessary and sufficient for stress-induced decreases in reward seeking behavior, elucidating a key circuit-level mechanism underlying stress-induced anhedonia.

neuroscience↗