`Auditory cortical micro-organization and its modulation by the orbitofrontal cortex’.

Sensory areas of the cerebral cortex show topographic organization of functional properties. Organization and neuronal response properties are known to change through attention, emotional and behavioral relevance of sensory stimuli. Such plasticity is likely orchestrated by top-down neuromodulatory signals dynamically shaping perception. Since perception is innately linked with cognitive processes the two need to be studied in conjunction. Particularly in the primary auditory cortex (ACX) progression of frequency selectivity (tonotopy) is the dominant
organizational feature, while other feature-based organizations are largely unknown. In this study, the functional micro-circuitry of layer II/III cells in the mouse ACX on the single cell level is probed using in-vivo 2-photon Ca2+ imaging. Tonotopy is found to be present on a large-scale but neuronal tuning properties are highly heterogeneous on a fine-scale. However, in the micro-scale, based on the spatial gradient of tuning properties of neurons, we find micro-organization based on harmonically related frequencies, which is the first evidence for micro-organization in the primary auditory cortex. We next investigate dynamic modulation of response properties and such organization based on inputs from orbitofrontal cortex (OFC) within the prefrontal cortex an
area known to be involved in reward based learning, decision-making, attention and reward associations. Also based on anatomical and functional reciprocal connectivity of OFC with sensory areas and other neuro-modulatory regions it is a primary candidate for orchestrating dynamic sensory plasticity required for such adaptive sensory processing and subsequently behavior. With micro stimulation of OFC paired with sound stimulation at particular frequencies we find remarkable rapid enhancement of tuning properties of neurons within ACX specific to the pairing frequency, which changes the functional micro-organization within the ACX. Thus OFC plays a role in mediating auditory cortical plasticity in the form of changes in tuning properties of
auditory cortical neurons. Collectively, these experiments provide insight into topographic organization in ACX and how such organization changes through top-down control of auditory processing. Current experiments are investigating the role of inhibitory neurons in functional organization and in mediation of top down plasticity in the ACX. Further work on origins of OFC activation during learning and the circuitry/pathways involved in driving such rapid plasticity will shed light on the mechanisms underlying perceptual, cognitive and learning deficits associated with OFC dysfunction occurring in a milieu of mild to severe neuropsychiatric disorders.