Central processing of auditory signals is strongly modulated by “top-down” (corticofugal) mechanisms that originate with brainstem-projecting neurons in primary auditory cortex (A1) and project, via long-range axons, to subcortical auditory centers. The corticocollicular (CCol) projection, from A1 to the inferior colliculus (IC), is a major corticofugal pathway. While the functions of this CCol pathway have been studied at the level of the IC, they are poorly understood at the level of A1. In particular, the properties of intracortical excitatory synaptic inputs that activate CCol neurons are unknown, as is the in vivo activity of these neurons during auditory stimulation. Here we propose an experimental program designed to elucidate the synaptic and in vivo properties of identified CCol neurons in A1. We will approach this overall goal using the mouse as our experimental model, retrograde labeling, and targeted opto-physiological recordings from A1 projection neurons. In addition to recording from CCol neurons, for comparison we will also target recordings to another distinct class of layer 5 pyramidal neurons, corticocortical (CCtx) neurons projecting across the corpus callosum to the contralateral A1. Our guiding hypothesis is that CCol and CCtx are differentially activated through projection-specific activity-dependent mechanisms. Our aims are: (1) Determine the synaptic properties of excitatory synaptic inputs from layer 2/3 pyramidal neurons onto labeled CCol and CCtx neurons. (2) Determine the in vivo activity of labeled CCol and CCtx neurons. The proposed research program is highly innovative, we believe, because it brings together powerful new techniques to tackle an important, but experimentally previously inaccessible, issue in the field of auditory research: the specific cellular mechanisms, and the specific in vivo activity patterns, involved in corticofugal and corticocortical communication from A1 to downstream networks. The proposed research is significant because it will provide basic new knowledge about the cortical mechanisms underlying top-down modulation of auditory processing.
|Effective start/end date||4/1/14 → 3/31/17|
- University of Pittsburgh (0033928 (124432-1) A1//R56DC013272)
- National Institute on Deafness and Other Communication Disorders (0033928 (124432-1) A1//R56DC013272)