Abstract
Despite their essential roles in signal processing in the brain, the functions of interneurons currently remain unclear in humans. We recently developed a method using the prepulse inhibition of sensory evoked cortical responses for functional measurements of interneurons. When a sensory feature is abruptly changed in a continuous sensory stimulus, change-related cortical responses are recorded using MEG. By inserting a weak change stimulus (prepulse) before the test change stimulus, it is possible to observe the inhibition of the test response. By manipulating the prepulse–test interval (PTI), several peaks appear in inhibition, suggesting the existence of temporally distinct mechanisms. We herein attempted to separate these components through the oral administration of diazepam and baclofen. The test stimulus and prepulse were an abrupt increase in sound pressure in a continuous click train of 10 and 5 dB, respectively. The results obtained showed that the inhibition at PTIs of 10 and 20 ms was significantly greater with diazepam than with the placebo administration, suggesting increased GABAA-mediated inhibition. Baclofen decreased inhibition at PTIs of 40 and 50 ms, which may have been due to the activation of GABAB autoreceptors. Therefore, the present study separated at least two inhibitory mechanisms pharmacologically.
Highlights
The outputs of a neural circuit are influenced by the balance between excitation and inhibition produced by pyramidal cells and interneurons, respectively
The results of the present study showed enhanced prepulse inhibition (PPI) at 10- and 20-ms prepulse–test interval (PTI) following the administration of diazepam, suggesting that GABAA receptors are involved in short-latency inhibition
PPI at the 10-ms PTI did not significantly suppressed the test response in the present study, the difference was significant in our previous study [11], suggesting that the inhibitory effects of prepulses with short PTIs were weak, their actions became obvious in the presence of diazepam
Summary
The outputs of a neural circuit are influenced by the balance between excitation and inhibition produced by pyramidal cells and interneurons, respectively. Despite their crucial roles in signal processing, the functions of interneurons remain largely unknown in humans mainly due to methodological limitations associated with the observation of their activities. There is currently no method to record IPSPs in their pure form in humans. This recording in vivo is challenging in animals.
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