Appropriate behavioral responses to acoustic stimuli involve coding of the physical properties of stimuli by the auditory system, as well as modification of coded information by diffuse neuromodulatory systems that are activated in specific behavioral states. Conversely, disruption of auditory pathways by injury, or degeneration of diffuse modulatory systems in pathological conditions (e.g., Alzheimer's disease) can disrupt appropriate responses. The long-term objectives of this research are to understand the cellular mechanisms and neuromodulatory regulation of information processing in auditory cortex. The experiments involve intracellular recordings to examine subthreshold synaptic integration of auditory inputs, and cholinergic modulation of tone-evoked synaptic potentials, in physiologically and morphologically identified neurons. Data is obtained using the whole-cell recording technique, which enables stable, high resolution intracellular recordings in vivo. Synaptic transmission is manipulated in single neurons via intracellular dialysis with pharmacological agents. Neurons are characterized electro- physiologically by determining intrinsic firing patterns, and morphologically by intracellular labeling with biocytin.
Specific aims i nclude determining how four synaptic potentials -- tow mediated by glutamate and two by gamma-aminobutyric acid (GABA) -- generate frequency receptive fields and rate-level functions. In part, contributions of GABAergic inhibition are revealed by intracellular blockade of membrane channels coupled to GABA receptors.
Specific aims also include determining how cholinergic neuromodulation modifies synaptic interactions. Stimulation of nucleus basalis cholinergic neurons that project to auditory cortex, or selective lesion of these neurons using the novel immunotoxin 192 IgG-saporin, test the hypothesis that cholinergic inputs modify synaptic integration to """"""""sharpen"""""""" frequency receptive fields. Neurons are thus characterized in terms of morphology, intrinsic membrane physiology, synaptic physiology, and acoustic responsiveness. This detailed, multifaceted characterization will promote an integrated, mechanistic understanding of auditory cortex function, and hence, lead to improved treatments for auditory cortex dysfunction.
| Metherate, Raju (2011) Functional connectivity and cholinergic modulation in auditory cortex. Neurosci Biobehav Rev 35:2058-63 |
