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

Abstract

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.

Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

“…Current sinks thereby correspond to the activity of excitatory synaptic populations, while current sources mainly reflect balancing return currents. Early synaptic thalamocortical inputs persist after intracortical silencing with the GABA A agonist muscimol related to thalamocortical projections on cortical layers III/IV and Vb/VIa (Happel et al 2010;Happel & Ohl, 2017;Brunk et al 2019) in accordance with reports by others (Schaefer et al 2015). Early current sinks in the auditory cortex are therefore indicative of thalamic input in granular layers III/IV and infragranular layers Vb/VIa (Szymanski et al 2009;Happel et al 2010).…”

Source identity shapes spatial preference in primary auditory cortex during active navigation

“…This finding is in line with earlier studies that found A1 neurons to encode task choice (Selezneva et al, 2006;Francis et al, 2018;Guo et al, 2019), and could also be associated with predictive processing (Keller and Mrsic-Flogel, 2018) and reward expectancy (Poort et al, 2015). Ventral tegmental area (VTA) is a possible source for such reward signaling inputs via direct dopaminergic connections to infragranular layers of A1 (Brunk et al, 2019). Such dopaminergic neurons have been shown to encode reward probability, and their response magnitude to predict changes in behaviour (Babayan et al, 2018), which might be the mechanism underlying the decision of staying or leaving in the target island in our paradigm.…”

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

“…The CSD thus provides a functional readout of the cortical microcircuitry function, encompassing a wider, mesoscopic field of view than for instance single-or multiunit approaches 55 . Early current sinks in the auditory cortex are, therefore, indicative of thalamic input in granular layers III/IV and infragranular layers Vb/VI 21,[56][57][58][59] . In order to describe the overall columnar processing, the CSD profiles were transformed by averaging the rectified waveforms of each channel:…”