Separate Functional Subnetworks of Excitatory Neurons Show Preference to Periodic and Random Sound Structures.

Auditory cortex (ACX) neurons are sensitive to spectro-temporal sound patterns and violations in patterns induced by rare stimuli embedded within streams of sounds. We investigate the auditory cortical representation of repeated presentations of sequences of sounds with standard stimuli (common) with an embedded deviant (rare) stimulus in two conditions, Periodic (Fixed deviant position) or Random (Random deviant position). We used extracellular single-unit and two-photon Ca2+ imaging recordings in layer 2/3 neurons of the mouse (Mus musculus) ACX of either sex. Population single-unit average responses increased over repetitions in the Random condition and were suppressed or did not change in the Periodic condition, showing general irregularity preference. A subset of neurons showed the opposite behavior, indicating regularity preference. Furthermore, pairwise noise correlations were higher in the Random condition than in the Periodic condition, suggesting a role of recurrent connections in the observed differential adaptation. Functional two-photon Ca2+ imaging showed that excitatory (EX), and inhibitory (IN) neurons [parvalbumin-positive (PV) and somatostatin-positive (SOM)] also had different categories of long-term adaptation as observed with single-units. However, examination of functional connectivity between pairs of neurons of different categories showed that EX-PV connected pairs behaved opposite to the EX-EX and EX-SOM pairs, with more connections outside category in Random condition than Periodic condition. Finally, considering Regularity, Irregularity, and no preference of connected pairs of neurons showed that EX-EX and EX-SOM pairs were in largely separate functional subnetworks with different preferences, not EX-PV pairs. Thus, separate subnetworks underlie coding of periodic and random sound sequences.SIGNIFICANCE STATEMENT Studying how the auditory cortex (ACX) neurons respond to streams of sound sequences help us understand the importance of changes in dynamic acoustic noisy scenes around us. Humans and animals are sensitive to regularity and its violations in sound sequences. Psychophysical tasks in humans show that the auditory brain differentially responds to Periodic and Random structures, independent of the listener's attentional states. Here, we show that mouse ACX L2/3 neurons detect changes and respond differently to patterns over long-time scales. The differential functional connectivity profile obtained in response to two different sound contexts suggests the vital role of recurrent connections in the auditory cortical network. Furthermore, the excitatory-inhibitory neuronal interactions can contribute to detecting the changing sound patterns.

Earliest Experience of a Relatively Rare Sound But Not a Frequent Sound Causes Long-Term Changes in the Adult Auditory Cortex.

Sensory experience during a critical period alters sensory cortical responses and organization. We find that the earliest sound-driven activity in the mouse auditory cortex (ACX) starts before ear-canal opening (ECO). The effects of auditory experience before ECO on ACX development are unknown. We find that in mouse ACX subplate neurons (SPNs), crucial in thalamocortical maturation, respond to sounds before ECO showing oddball selectivity. Before ECO, SPNs are more selective to oddball sounds in auditory streams than thalamo-recipient layer 4 (L4) neurons and not after ECO. We hypothesize that SPN's oddball selectivity can direct the development of L4 responses before ECO. Exposing mice, of either sex, before ECO to a rarely occurring tone in a stream of another tone occurring frequently leads to strengthening the adult cortical representation of the rare tone, but not that of the frequent tone. Results of control exposure experiments at multiple developmental windows that also use only a single tone corroborate the observations. We further explain the strengthening of deviant inputs before ECO and not after ECO using a binary network model mimicking the hierarchical structure of subplate and L4 neurons and response properties derived from our data, with synapses following Hebbian spike time-dependent plasticity learning rule. Information-theoretic analysis with sparse coding assumptions also predicts the observations. Thus, relatively salient low probability sounds in the earliest auditory environment cause long-term changes in the ACX.SIGNIFICANCE STATEMENT Early auditory experience can change the organization and responses of the auditory cortex in adulthood. However, little is known about how auditory experience at prenatal ages changes neural circuits and response properties. In mice at equivalent early developmental stages, we find that auditory experience of a particular kind, with a less frequently occurring sound in a stream of another sound, alters adult cortical responsiveness, specifically of the less frequent sound. However, at the previously known critical period of development, the opposite is observed, where the more frequent sound's representation is strengthened in the adult compared with the less frequent sound. We thus show that a specific type of auditory environment can influence adult auditory processing at the earliest ages.