Intracortical Circuits Amplify Sound-evoked Activity in Primary Auditory Cortex following 2 Systemic Injection of Salicylate in the Rat 3 Authors 4

27 A high dose of sodium salicylate temporarily induces tinnitus, mild hearing loss, and 28 possibly hyperacusis in humans and other animals. Salicylate has well-established effects on 29 cochlear function, primarily resulting in the moderate reduction of auditory input to the brain. 30 Despite decreased peripheral sensitivity and output, salicylate induces a paradoxical 31 enhancement of the sound-evoked field potential at the level of auditory cortex. Previous 32 electrophysiological studies have begun to characterize changes in thalamorecipient layers of 33 A1; however, A1 is a complex neural circuit with recurrent intracortical connections. In order to 34 describe the effects of acute systemic salicylate treatment on both thalamic and intracortical 35 sound-driven activity across layers of A1, we applied current-source density (CSD) analysis to 36 field potentials sampled across cortical layers in the anesthetized rat. CSD maps were normally 37 characterized by a large, short latency, monosynaptic, thalamically-driven sink in granular layers 38 followed by a lower amplitude, longer latency, polysynaptic, intracortically-driven sink in 39 supragranular layers. Following systemic administration of salicylate, there was a near doubling 40 of both granular and supragranular sink amplitudes at higher sound levels. The supragranular 41 sink amplitude input/output function changed from becoming asymptotic at ~50 dB to sharply 42 non-asymptotic, often dominating the granular sink amplitude at higher sound levels. The 43 supragranular sink also exhibited a significant decrease in peak latency reflecting an 44 acceleration of intracortical processing of the sound-evoked response. Additionally, multiunit 45 (MU) activity was altered by salicylate; the normally onset/sustained MU response type was 46 transformed into a primarily onset response type in granular and infragranular layers. The 47 results from CSD analysis indicate that salicylate significantly enhances sound-driven response 48 via intracortical circuits. 49