A developmental cell-type switch in cortical interneurons leads to a selective defect in cortical oscillations

Area of Science:

• Neuroscience
• Cellular Biology
• Cortical Circuitry

Background:

• Interneurons in the neocortex exhibit cellular diversity, suggesting subtype-specific roles in cortical inhibition.
• Understanding compensatory mechanisms for interneuron loss is crucial for comprehending cortical development and function.

Purpose of the Study:

• To investigate whether the loss of parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons can be compensated for during cortical development.
• To determine the specific contributions of PV+ and SST+ interneurons to synaptic currents, receptive fields, inhibitory synchronization, and gamma oscillations.

Main Methods:

• Utilized a genetic cell fate switch to selectively delete PV+ and SST+ interneurons in cortical layers 2-4.
• Maintained a constant total interneuron population to isolate the effects of specific subtype loss.
• Assessed synaptic currents, receptive fields (RFs), in vitro inhibitory synchronization, and in vivo cortical gamma oscillations.

Main Results:

• Compensatory mechanisms were observed at the level of synaptic currents and somatosensory cortex receptive fields.
• A significant deficit in inhibitory synchronization in vitro and a marked reduction in cortical gamma oscillations in vivo were identified.
• These deficits were linked to the loss of specific interneuron subtypes, particularly PV+ interneurons.

Conclusions:

• Cortical inhibitory/excitatory balance and receptive field properties can be maintained through compensatory roles of multiple interneuron subtypes.
• Cortical gamma oscillations are critically dependent on the unique cellular properties of specific interneuron subtypes, likely the fast signaling of PV+ interneurons.
• This highlights a non-compensable role for PV+ interneurons in generating robust gamma oscillations.