Properties of the Caudal Pontine Reticular Nucleus Neurons Determine the Acoustic Startle Response in KO Rats.

BACKGROUND

Rats with a loss-of-function mutation in the contactin-associated protein-like 2 () gene have been validated as an animal model of autism spectrum disorder (ASD). Similar to many autistic individuals, knock-out rats () are hyperreactive to sound as measured through the acoustic startle response. The brainstem region that mediates the acoustic startle response is the caudal pontine reticular nucleus (PnC), specifically giant neurons in the PnC. We previously reported a sex-dependent genotypic effect in the sound-evoked neuronal activity recorded from the PnC, whereby female rats had a dramatic increase in sound-evoked responses compared with wildtype counterparts, but male rats showed only a modest increase in PnC activity that cannot fully explain the largely increased startle in male rats. The present study therefore investigates activation and histological properties of PnC giant neurons in rats and wildtype littermates.

METHODS

The acoustic startle response was elicited by presenting rats with 95 dB startle pulses before rats were euthanized. PnC brain sections were stained and analyzed for the total number of PnC giant neurons and the percentage of giant neurons that expressed phosphorylated cAMP response element binding protein (pCREB) in response to startle stimuli. Additionally, electrophysiology was conducted to assess the resting state activity and intrinsic properties of PnC giant neurons.

RESULTS

Wildtype and rats had similar total numbers of PnC giant neurons and similar levels of baseline pCREB expression, as well as similar numbers of giant neurons that were firing at rest. Increased startle magnitudes in rats were associated with increased percentages of pCREB-expressing PnC giant neurons in response to startle stimuli. Male rats had increased pCREB-expressing PnC giant neurons compared with female rats, and the recruited giant neurons in males were also larger in soma size.

CONCLUSIONS

Recruitment and size of PnC giant neurons are important factors for regulating the magnitude of the acoustic startle response in rats, particularly in males. These findings allow for a better understanding of increased reactivity to sound in rats and in -associated disorders such as ASD.