Cosyne 2007 Friday evening, Poster II-52 Neuromodulation and plasticity of the adult auditory cortex RC Froemke1, P Levis2, MM Merzenich1, CE Schreiner1 1: Coleman Lab, Keck Center, Dept. Otolaryngology, UCSF, CA, USA 2:Computer Systems Lab, Depts. EE & CS, Stanford University, Palo Alto, CA, USA Cortical networks are highly dynamic and labile. In large part, these qualities reflect the ability of cortical synapses to be rapidly modified in a way that depends on the patterns of experience, activity, and neuromodulation. However, the rules of cortical synaptic plasticity and neuromodulation remain unclear, especially in the intact brain, where cortical circuitry is under the powerful influence of a diverse set of subcortical systems. To understand how neuronal activity and neuromodulation lead to changes in cortical synapses in vivo, we have used a combination of approaches, including in vivo whole-cell recording, electrical stimulation of the cortex, thalamus, and subcortical neuromodulator nuclei, and telemetric recording and stimulation in the behaving animal. In the experiments reported here, we have focused on the organization of receptive fields in the primary auditory cortex (A1) of adult rats, and the control of cortical responses by modulatory inputs from the basal forebrain. Our whole-cell recording experiments first showed that sensory stimulation alone does not lead to long-term changes in synaptic receptive fields, suggesting that repetitive pre- and postsynaptic spiking (such as that which drives spike-timing-dependent plasticity) are not sufficient for long- term synaptic modification in adult A1 in vivo. However, pairing sensory stimulation with electrical stimulation of the basal forebrain, containing the major cholinergic input to the cortex, reliably produced large long-term changes in the synaptic receptive fields of A1 neurons. Excitatory currents were enhanced concomitantly with suppression of inhibitory currents, and these effects were specific to the paired stimulus. While the potentiation of excitation persisted for the duration of the recording, the suppression of inhibition recovered in an activity-dependent manner over a few hours, eventually increasing to ‘re-balance’ the excitatory and inhibitory synaptic receptive fields. Simultaneous monitoring of cortical and thalamic inputs via electrical stimulation revealed that these changes are intrinsic to the cortex. Parallel studies using wireless recording and stimulation in the behaving animal have shown the effects of basal forebrain stimulation on auditory discrimination. Our results explain how neuromodulation can changes spike rates and cortical maps, can boosts attention and behavioral performance, and account for the necessity of neuromodulation to drive long-term cortical plasticity in the adult brain. 125.