Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits.

The primary auditory cortex (A1) is an essential, integrative node that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision-making. However, the realization of this integration with respect to the cortical microcircuitry is not well understood. Here, we characterize layer-specific, spatiotemporal synaptic population activity with chronic, laminar current source density analysis in Mongolian gerbils (Meriones unguiculatus) trained in an auditory decision-making Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task- and choice-related information is represented in the mesoscopic neuronal population code of A1. Based on generalized linear-mixed effect models we found a layer-specific and multiplexed representation of the task rule, action selection, and the animal's behavioral options as accumulating evidence in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit in the sensory cortex in order to code task-relevant information and guide sensory-based decision-making.

Learning Induces Transient Upregulation of Brevican in the Auditory Cortex during Consolidation of Long-Term Memories.

It is a daily challenge for our brains to establish new memories via learning while providing stable storage of remote memories. In the adult vertebrate brain, bimodal regulation of the extracellular matrix (ECM) may regulate the delicate balance of learning-dependent plasticity and stable memory formation. Here, we trained adult male mice in a cortex-dependent auditory discrimination task and measured the abundance of ECM proteins brevican (BCN) and tenascin-R over the course of acquisition learning, consolidation, and long-term recall in two learning-relevant brain regions; the auditory cortex and hippocampus. Although early training led to a general downregulation of total ECM proteins, successful retrieval correlated with a region-specific and transient upregulation of BCN levels in the auditory cortex. No other parameter such as arousal or stress could account for the transient and region-specific BCN upregulation. This performance-dependent biphasic regulation of the ECM may assist transient plasticity to facilitate initial learning and subsequently promote the long-term consolidation of memory.SIGNIFICANCE STATEMENT The capacity to learn throughout life and at the same time guarantee lifelong storage and remote recall of established memories is a daily challenge. Emerging evidence suggests an important function of the extracellular matrix (ECM), a conglomerate of secreted proteins and polysaccharides in the adult vertebrate brain. We trained mice in an auditory long-term memory task and measured learning-related dynamic changes of the ECM protein brevican. Specifically, in the auditory cortex brevican is downregulated during initial learning and subsequently upregulated in exclusively those animals that have learned the task, suggesting a performance-dependent regulation in the service of memory consolidation and storage. Our data may provide novel therapeutic implications for several neuropsychiatric diseases involving dysregulation of the ECM.

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex.

Reward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. Yet, it is unknown, how the VTA influences cortical frequency processing and spectral integration. Therefore, we investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils. While auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects persisted over more than 30 minutes after VTA stimulation. Altogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. We thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.