Auditory cortex ensembles jointly encode sound and locomotion speed to support sound perception during movement

Abstract

The ability to process and act upon incoming sounds during locomotion is critical for survival and adaptive behavior. Despite the established role that the auditory cortex (AC) plays in behavior- and context-dependent sound processing, previous studies have found that auditory cortical activity is on average suppressed during locomotion as compared to immobility. While suppression of auditory cortical responses to self-generated sounds results from corollary discharge, which weakens responses to predictable sounds, the functional role of weaker responses to unpredictable external sounds during locomotion remains unclear. In particular, whether suppression of external sound-evoked responses during locomotion reflects reduced involvement of the AC in sound processing or whether it results from masking by an alternative neural computation in this state remains unresolved. Here, we tested the hypothesis that rather than simple inhibition, reduced sound-evoked responses during locomotion reflect a tradeoff with the emergence of explicit and reliable coding of locomotion velocity. To test this hypothesis, we first used neural inactivation in behaving mice and found that the AC plays a critical role in sound-guided behavior during locomotion. To investigate the nature of this processing, we used two-photon calcium imaging of local excitatory auditory cortical neural populations in awake mice. We found that locomotion had diverse influences on activity of different neurons, with a net suppression of baseline-subtracted sound-evoked responses and neural stimulus detection, consistent with previous studies. Importantly, we found that the net inhibitory effect of locomotion on baseline-subtracted sound-evoked responses was strongly shaped by elevated ongoing activity that compressed the response dynamic range, and that rather than reflecting enhanced “noise,” this ongoing activity reliably encoded the animal’s locomotion speed. Decoding analyses revealed that locomotion speed and sound are robustly co-encoded by auditory cortical ensemble activity. Finally, we found consistent patterns of joint coding of sound and locomotion speed in electrophysiologically recorded activity in freely moving rats. Together, our data suggest that rather than being suppressed by locomotion, auditory cortical ensembles explicitly encode it alongside sound information to support sound perception during locomotion.

Multimodal mismatch responses in mouse auditory cortex

“…While doing this, we recorded activity in L2/3 neurons of ACx using two-photon calcium imaging. Using this approach, we first confirmed that a substantial subset of L2/3 neurons in ACx responds to either auditory, visual (Sharma et al, 2021), or motor-related inputs (Henschke et al, 2021; Morandell et al, 2023; Vivaldo et al, 2023). While we found that L2/3 neurons in ACx responded to audiomotor mismatches in a way that closely resembles visuomotor mismatch responses found in V1 (Keller et al, 2012), we found no evidence of responses to visuomotor mismatch in ACx.…”

“…Finally, we investigated how running modulates auditory and visual responses in ACx. In V1, running strongly increases responses to visual stimuli (Niell and Stryker, 2010), while in auditory cortex running has been shown to modulate auditory responses in a variety of different ways (Audette et al, 2022; Bigelow et al, 2019; Henschke et al, 2021; McGinley et al, 2015; Morandell et al, 2023; Schneider et al, 2014; Vivaldo et al, 2023; Yavorska and Wehr, 2021; Zhou et al, 2014). Separating auditory responses by running state, we found that sound evoked responses of ACx neurons were overall similar during sitting and running, but exhibited a smaller decrease in activity when the mouse was sitting ( Figure S1A ).…”

“…Consistent with previous reports, we found that auditory, visual, and motor-related signals are intermixed in the population of L2/3 neurons in ACx. Responses to both motor-related (McGinley et al, 2015; Schneider et al, 2014; Vivaldo et al, 2023; Yavorska and Wehr, 2021; Zhou et al, 2014) and visual signals (Bigelow et al, 2022; Morrill and Hasenstaub, 2018; Sharma et al, 2021) have been reported across layers in ACx, with the strongest running modulation effect found in L2/3 (Schneider et al, 2014). Also, consistent with previous reports, we found that a subset of L2/3 neurons in ACx respond to audiomotor prediction errors (Audette et al, 2022; Liu and Kanold, 2022).…”

A Cortico-Striatal Circuit for Sound-Triggered Prediction of Reward Timing

“…Similar to our findings in the first cohort (Figure 1), animals in this cohort also changed the rate of their predictive licking curves according to the duration of the sound-reward intervals, with the slope increasing with increased interval durations for both rewarded and catch trials (Figure 4B and C, p = 0.0000544 for rewarded trials and p = 0.00012 for catch trials; Kruskal-Wallis test for group differences). We similarly identified the best behavior performance day of each sound-reward interval for analysis and excluded trials in which the animal moved or in which the animal licked in the 200 ms period from sound onset to avoid a contribution of motor activity to the sound response magnitude (Schneider et al, 2014; Vivaldo et al, 2023; Whitton et al, 2014). We then quantified the magnitude of the AC responses to the sound for each of the interval durations per animal.…”

“…In the auditory pathway, a key candidate brain region for encoding sound-triggered timing is the auditory cortex (AC), due to its established role in behavior-and decision-makingdependent sound processing (Bathellier et al, 2012;Francis et al, 2018;Fritz et al, 2003Fritz et al, , 2005King & Schnupp, 2007;Lee & Rothschild, 2021;Nelken et al, 2014;Town et al, 2018;Vivaldo et al, 2023). Numerous studies have demonstrated retrospective coding of the degree to which a sound deviates from expectation in AC (Heilbron & Chait, 2018;Khouri & Nelken, 2015;Rubin et al, 2016;Taaseh et al, 2011;Ulanovsky et al, 2003Ulanovsky et al, , 2004Yaron et al, 2012).…”