Project Summary
The auditory midbrain (inferior colliculus, IC) is a hub and a major subcortical integration center in the central
auditory pathway. Neurons in the IC are tuned to specific spectro-temporal features and are involved in the
processing of communication sounds and speech. Abnormal sound-evoked or spontaneous IC activity has
been associated with numerous central hearing dysfunctions including impaired speech perception,
hyperacusis, and tinnitus. The spectro-temporal tuning of IC neurons arises from the integration of a multitude
of ascending and descending inputs and an elaborated network of excitatory and inhibitory intrinsic synaptic
connections between IC neurons. While the function and organization of external inputs to the IC are becoming
increasingly understood, current understanding of the organization, physiology, and development of synaptic
connections intrinsic to the IC is limited, hampering insight into their potential roles in IC function. To fill this
knowledge gap, we propose to address three specific Aims. In Aim 1 we will test the hypothesis that the central
nucleus of the IC (CNIC) contains two separate, functionally distinct, local networks arising from disc-shaped
and stellate cells. We further hypothesize that the differentiation of these networks occurs after hearing onset
requires normal patterns or levels of sound-evoked activity. To address these hypotheses, we will use laser
scanning photostimulation with caged glutamate to map the location of neurons in the CNIC that
monosynaptically connect to identified CNIC neurons in slices from control mice and from mice that were
reared in pulsed white noise or have experienced temporary conductive hearing loss. In Aim 2 we will test the
hypothesis that the physiological properties of synaptic connections are distinct between the two intrinsic CNIC
networks and that their maturation depends on normal auditory experience. We will address this using
simultaneous whole-cell recordings from identified neurons in slices from control mice and mice with a history
of abnormal auditory experience. In Aim 3 we will test the hypothesis that abnormal sound-evoked single unit
responses in the CNIC of mice with a history of abnormal auditory experience reflect abnormal intrinsic
connections. We will address this by characterizing spectro-temporal responses properties of optogenetically
identified glutamatergic and GABAergic CNIC neurons in awake control mice and mice with a history of
abnormal auditory experience and correlate the changes observed in in-vivo with changes in intrinsic networks
characterized in-vitro. Results from the proposed project will provided novel insight into the organization,
synaptic physiology, and development of intrinsic CNIC circuits and their possible role in impaired sound
processing in the CNIC. This new information will be valuable for understanding the circuit changes in the
CNIC that contribute to the generation of central hearing deficits that are commonly observed in children that
suffered from conductive hearing loss.