The general goal of this project is to understand how information about sound is processed by the brain. The inferior colliculus (IC) is the main auditory structure in the midbrain. All information about sound must pass through the IC as it travels from the ear to the cerebral cortex. This project continues our effort to understand the cellular basis for function of the IC. Despite numerous studies, far too little is known about how microanatomy, neuronal specializations, and synaptic organization underlie auditory processing in the IC. There are two very different types of excitatory input on neurons in the IC. We have discovered that specialized "calyx-like" axosomatic synapses occur on the large GABAergic neurons in IC. These synapses contain VGLUT2, a molecule that loads the transmitter glutamate into synaptic vesicles. These excitatory synapses are absent on excitatory neurons or smaller GABAergic neurons where dendritic excitatory synapses predominate. Two basic circuits in the IC are proposed. In one, large GABAergic IC neurons receive a dense, excitatory synaptic input on the cell body and proximal dendrites. The other circuit has smaller glutamatergic and GABAergic IC neurons with glutamatergic inputs only on dendrites. GABAergic neurons in IC are studied in two experiments. We will show: (1) the large GABAergic neurons project exclusively to the thalamus;(2) the GABAergic neurons with and without calyx-like inputs will differ in their firing patterns and intrinsic membrane properties. Excitatory inputs to IC are studied in experiments to reveal the structure and function of the VGLUT2 calyx-like input to the large GABAergic IC neurons (circuit 1). We will show: (3) segregated auditory brainstem neurons expressing VGLUT1 or VGLUT2 that project to IC;(4) VGLUT2 axosomatic synapse originates from a single source in the auditory brainstem, and that this specialized synapse comes from a single axon;and (5) the VGLUT2 axosomatic synapses on GABAergic neurons differ from other glutamate synapses in IC. Inhibitory Inputs. Brain circuitry in the IC is notable because the IC receives both inhibitory and excitatory inputs from the lower auditory brainstem. The excitatory inputs to the IC are segregated into functional zones, but it is not clear if inhibitory inputs also follow the same pattern. Here, in experiment 6, we will use auditory physiology with an uanesthetized rabbit preparation to relate the patterns of inhibitory input to neural responses in the IC. We will specifically test the hypothesis that the ICc domains have different patterns of inhibitory inputs.
The inferior colliculus is important for normal hearing since it is a major part of the central auditory pathway and neurons from the auditory cortex to the cochlear nucleus send direct connections to the inferior colliculus. Pathology such as stroke or tumor in the inferior colliculus may contribute to deafness, hearing loss, or audiogenic seizures. The inferior colliculus is now the site of auditory midbrain implants to electrically stimulate the central auditory pathway in patients after surgical removal of the eighth nerve.
|Ito, Tetsufumi; Oliver, Douglas L (2014) Local and commissural IC neurons make axosomatic inputs on large GABAergic tectothalamic neurons. J Comp Neurol 522:3539-54|
|Ono, Munenori; Oliver, Douglas L (2014) The balance of excitatory and inhibitory synaptic inputs for coding sound location. J Neurosci 34:3779-92|
|Ito, Tetsufumi; Bishop, Deborah C; Oliver, Douglas L (2011) Expression of glutamate and inhibitory amino acid vesicular transporters in the rodent auditory brainstem. J Comp Neurol 519:316-40|
|Oliver, D L; Izquierdo, M A; Malmierca, M S (2011) Persistent effects of early augmented acoustic environment on the auditory brainstem. Neuroscience 184:75-87|
|Loftus, William C; Bishop, Deborah C; Oliver, Douglas L (2010) Differential patterns of inputs create functional zones in central nucleus of inferior colliculus. J Neurosci 30:13396-408|
|Tong, Huaxia; Steinert, Joern R; Robinson, Susan W et al. (2010) Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the trapezoid body maintained in organotypic culture. J Physiol 588:1451-68|
|Izquierdo, M A; Oliver, D L; Malmierca, M S (2009) [Functional and activity-dependent plasticity mechanisms in the adult and developing auditory brain] Rev Neurol 48:421-9|
|Ito, Tetsufumi; Bishop, Deborah C; Oliver, Douglas L (2009) Two classes of GABAergic neurons in the inferior colliculus. J Neurosci 29:13860-9|
|Loftus, W C; Malmierca, M S; Bishop, D C et al. (2008) The cytoarchitecture of the inferior colliculus revisited: a common organization of the lateral cortex in rat and cat. Neuroscience 154:196-205|
|Altschuler, R A; Tong, L; Holt, A G et al. (2008) Immunolocalization of vesicular glutamate transporters 1 and 2 in the rat inferior colliculus. Neuroscience 154:226-32|
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