Altered prefrontal and cerebellar parvalbumin neuron counts are associated with cognitive changes in male rats

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Autism Spectrum Disorder Research

Background:

• Prenatal exposure to valproic acid (VPA), an anti-seizure medication, is a known risk factor for autism spectrum disorder (ASD).
• Individuals with ASD often exhibit structural and functional alterations in the cerebellum and medial prefrontal cortex (mPFC), including changes in Purkinje cells and excitatory/inhibitory balance.

Purpose of the Study:

• To investigate the effects of prenatal VPA exposure on inhibitory parvalbumin-expressing (PV+) neuron populations in the cerebellum and mPFC of rats.
• To assess the impact of these neurobiological changes on cognitive and anxiety-like behaviors in young adult rats.

Main Methods:

• Rats were exposed to a high dose of VPA during gestation.
• Cognitive and anxiety-like behaviors were evaluated using a set-shifting task and the elevated plus maze.
• Counts of PV+ neurons were quantified in the mPFC and specific cerebellar lobules (VI and VII).

Main Results:

• VPA-exposed males showed increased PV+ neuron counts in cerebellar lobule VII (crus I and II) and decreased PV+ neuron counts in the mPFC.
• Both male and female VPA-exposed rats exhibited increased PV+ Purkinje cell counts in cerebellar lobule VI.
• In males, increased PV+ Purkinje cells in lobule VI correlated with impaired performance on the intra-dimensional shifting task.

Conclusions:

• Prenatal VPA exposure alters inhibitory neuron development in cerebellar-frontal circuits.
• Increased Purkinje cell proliferation in lobule VI may underlie observed volume changes and cognitive deficits in VPA-exposed rats.
• These findings suggest that disrupted inhibitory signaling in these circuits contributes to ASD-related cognitive impairments.