Input-specific control of interneuron numbers in nascent striatal networks

Area of Science:

• Neuroscience
• Developmental Biology
• Circuit Assembly

Background:

• Establishing correct neuronal numbers is crucial for functional brain circuits.
• Mechanisms governing the relative proportions of distinct neuronal subtypes are largely unknown.
• Programmed cell death plays a role in shaping neuronal populations during development.

Purpose of the Study:

• To investigate the mechanisms establishing the proportions of parvalbumin-expressing (PV+) and cholinergic (ChAT+) interneurons in the developing mouse striatum.
• To determine if programmed cell death and afferent connectivity regulate interneuron subtype survival.

Main Methods:

• Analysis of programmed cell death in PV+ and ChAT+ interneurons during the first two postnatal weeks in mice.
• Investigation of the role of afferent connectivity (cortical and local) in regulating interneuron survival.

Main Results:

• Both PV+ and ChAT+ interneurons undergo significant programmed cell death postnatally.
• PV+ interneuron survival is regulated by long-range cortical inputs.
• ChAT+ interneuron survival is regulated by local inputs from medium spiny neurons.

Conclusions:

• Input-specific mechanisms differentially regulate the survival of distinct interneuron subtypes during development.
• Afferent connectivity plays a critical role in establishing the final numbers of interneurons in striatal networks.
• This study elucidates circuit-level control over neuronal population size during network formation.