Abstract.
21Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected 22 circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have 23 predicted that suppression of inhibition in such excitatory-inhibitory networks can lead to either an 24 increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on 25 stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex 26 could evoke such a variety of effects in tone-evoked responses and in behavioral frequency 27 discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus 28 selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting 29 differences in circuitry or expression of optogenetic factors. Changes in neural population 30 responses consistently predicted behavioral changes for individuals separately, including 31 improvement and impairment in acuity. This correlation between cortical and behavioral change 32 demonstrates that, despite complex and varied effects these manipulations can have on neuronal 33 dynamics, the resulting changes in cortical activity account for accompanying changes in 34 behavioral acuity.
36Author summary.
37Excitatory and inhibitory interactions determine stimulus specificity and tuning in sensory 38 cortex, thereby controlling perceptual discrimination acuity. Modeling of such excitatory-inhibitory 39 circuits has predicted that suppressing the activity of inhibitory neurons can lead to increases or, 40 paradoxically, decreases in excitatory activity, depending on the architecture and modulation 41 parameters of the inhibitory component of the network. Here, we capitalized on differences 42 between subjects to test whether suppressing/activating inhibition and excitation across a range 43 of parameters in sensory cortex can in fact exhibit such paradoxical effects for both stimulus 44 sensitivity and behavioral discriminability. Indeed, we found that the same optogenetic 45 manipulation in the auditory cortices of different mice could improve or impair frequency 46 discrimination acuity, in a fashion that was predictable from the effects on cortical responses to 47 tones. The same manipulations sometimes produced opposite changes in the behavior of 48 different individuals, supporting theoretical predictions for inhibition-stabilized networks.