Deep brain stimulation of the nucleus basalis magnocellularis ameliorates autistic behavior in a rat model of autism via cholinergic modulation in the prefrontal cortex.

OBJECTIVE

In the present study, we investigated whether deep brain stimulation (DBS) of the nucleus basalis magnocellularis (NBM) improves autism spectrum disorder (ASD)-related behavioral abnormalities in a valproic acid (VPA)-induced rat model of autism, consistent with changes in cholinergic markers in the medial prefrontal cortex (mPFC).

METHODS

On the 12.5th day of gestation, pregnant rats (n = 16) received a single intraperitoneal injection of 500 mg/kg sodium valproate dissolved in 0.9% saline, while others (n = 5) received saline alone. Male offspring were allowed to reach 3 months of age and then were randomly assigned to one of four experimental groups: Contr - prenatally saline injected, VPA - prenatally VPA-injected, VPA/I - VPA-injected with electrode implantation in the NBM, and VPA/S - VPA-injected with electrical stimulation. DBS was initiated in rats of the VPA/S group 10 days after surgery (two consecutive hours per day, every day for 2 weeks; DBS parameters: 60 Hz, 120 µs, and 50 µA).

RESULTS

The prenatally VPA-exposed rats demonstrate deficits in social behavior, increased locomotor activity, and reduced anxiety levels. Immunohistochemical evaluation shows a decrease in the number of acetylcholinesterase-immunoreactive neurons in the mPFC and choline acetyltransferase-immunoreactive neurons in the NBM. NBM-DBS improves VPA-induced autistic behavior and increases the number of acetylcholinesterase-immunoreactive neurons in the PFC.

CONCLUSION

The correlation between ASD-like behavior and cholinergic markers in the mPFC supports our hypothesis that NBM-DBS improves behavioral deficits by modulating cholinergic neurotransmission in the PFC in a rat model of autism.