Neuronal stimulus selectivity is shaped by feedforward and recurrent excitatory-inhibitory interactions. In the auditory cortex (AC), parvalbumin- (PVs) and somatostatin-positive (SOMs) inhibitory interneurons differentially modulate frequency-dependent responses of excitatory neurons. Responsiveness of neurons in AC to sounds is furthermore dependent on stimulus history. We found that inhibitory effects of SOMs and PVs diverged as a function of adaptation to temporal repetition of tones. Prior to adaptation, suppressing either SOM or PV inhibition drove both increases and decreases in excitatory spiking activity. After adaptation, suppressing SOM activity caused predominantly disinhibitory effects, whereas suppressing PV activity still evoked bi-directional changes. SOM, but not PV-driven inhibition, dynamically modulated frequency tuning with adaptation. Unlike PV-driven, SOM-driven inhibition elicited gain-like increases in frequency tuning reflective of adaptation. Our findings suggest that distinct cortical interneurons differentially shape tuning to sensory stimuli across the neuronal receptive field, altering frequency selectivity of excitatory neurons during adaptation.

The extensive feedback from the auditory cortex (AC) to the inferior colliculus (IC) supports critical aspects of auditory behavior but has not been extensively characterized. Previous studies demonstrated that activity in IC is altered by focal electrical stimulation and pharmacological inactivation of AC, but these methods lack the ability to selectively manipulate projection neurons. We measured the effects of selective optogenetic modulation of cortico-collicular feedback projections on IC sound responses in mice. Activation of feedback increased spontaneous activity and decreased stimulus selectivity in IC, whereas suppression had no effect. To further understand how microcircuits in AC may control collicular activity, we optogenetically modulated the activity of different cortical neuronal subtypes, specifically parvalbumin-positive (PV) and somatostatin-positive (SST) inhibitory interneurons. We found that modulating the activity of either type of interneuron did not affect IC sound-evoked activity. Combined, our results identify that activation of excitatory projections, but not inhibition-driven changes in cortical activity, affects collicular sound responses.

Graphical Abstract Highlights d Basolateral amygdala projects to the TRN gating signals to the cortex d BLA-TRN activation amplifies sound responses in the auditory thalamus and cortex d A model for the BLA-TRN-AC connectivity explains the results d This pathway is a potential target for treatment of emotional and sensory disorders SUMMARY Many forms of behavior require selective amplification of neuronal representations of relevant environmental signals. Emotional learning enhances sensory responses in the sensory cortex, yet the underlying circuits remain poorly understood.We identify a pathway between the basolateral amygdala (BLA), an emotional learning center in the mouse brain, and the inhibitory reticular nucleus of the thalamus (TRN). Optogenetic activation of BLA suppressed spontaneous, but not tone-evoked, activity in the auditory cortex (AC), amplifying tone-evoked responses. Viral tracing identified BLA projections terminating at TRN. Optogenetic activation of amygdala-TRN projections further amplified tone-evoked responses in the auditory thalamus and cortex. The results are explained by a computational model of the thalamocortical circuitry, in which activation of TRN by BLA primes thalamocortical neurons to relay relevant sensory input. This circuit mechanism shines a neural spotlight on behaviorally relevant signals and provides a potential target for the treatment of neuropsychological disorders.

The extensive feedback from the auditory cortex (AC) to the inferior colliculus (IC) supports critical aspects of auditory learning, but has not been extensively characterized. Furthermore, it remains unknown whether and how intra-cortical processing of auditory information propagates to earlier stages in the auditory pathway. Previous studies demonstrated that responses of neurons in IC are altered by focal electrical stimulation and pharmacological inactivation of auditory cortex, but these methods lack the ability to selectively manipulate the activity of projection neurons. Combining viral technology with electrophysiological recordings, we measured the effects of selective optogenetic activation or suppression of cortico-collicular feedback projections on IC responses to sounds. Activation of cortico-collicular feedback generally increased spontaneous activity and decreased stimulus selectivity in IC, whereas suppression of the feedback did not affect collicular activity. To further understand how microcircuits in the auditory cortex may control collicular activity, we tested the effects of optogenetically modulating different cortical neuronal subtypes, specifically parvalbumin-positive (PV) and somatostatin-positive (SOM) inhibitory interneurons. We found that, despite strong effects on sound-evoked responses across the layers of AC, activating either type of interneuron did not affect IC sound-evoked activity. However, suppression of SOMs, but not PVs, weakly increased spontaneous activity in IC. These findings suggest that shaping of sound responses mediated by cortical inhibition does not affect sound processing in IC. Combined, our results identify that activation of excitatory projections, but not inhibitory-driven increases in cortical activity, affects collicular sound responses. Significance StatementDescending projections from the auditory cortex to the auditory midbrain, the inferior colliculus, have been shown to play a critical role in auditory learning and behavior. However, little is known about the details of how this direct feedback shapes neuronal responses to sounds in the inferior colliculus. We found that direct activation of cortico-collicular feedback increased spontaneous and modulated sound-evoked activity in the inferior colliculus. Interestingly, modulation of inhibitory interneuron activity, thereby increasing or decreasing excitatory neuronal activity in the auditory cortex, did not affect sound responses in the inferior colliculus. This work offers evidence that auditory cortex shapes sound responses in the inferior colliculus via direct feedback independently of the activity of cortical inhibitory interneurons.

In the originally published version of this article, the duration of the DC stimulation to TRN and TC was stated as 100 ms and 10 ms, respectively. However, it should have been stated as 250 ms and 50 ms. The error has now been corrected online. The correct numbers were used to mimic the experiments. The simulation results, the conclusion, and the figure do not change.