Date

3-2015

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Unipolar brush cells (UBCs) are glutamatergic interneurons present in cerebellum-like structures. In mammals, they are found in cerebellum and the dorsal cochlear nucleus (DCN). They receive glutamatergic mossy fiber input on an elaborate brush-like dendrite, and relay multisensory signals to granule cells through a feedforward pathway. The first studies characterizing synaptic properties of cerebellar UBCs revealed a slow-decaying biphasic excitatory post-synaptic current (EPSC) that triggered a long train of postsynaptic action potentials. Thus, UBCs seemed to be amplifying multisensory signals from mossy fibers to their target granule cells. Immunohistochemical studies revealed two distinct UBC populations: calretinin+ UBCs and mGluR1α+ UBCs. Some of their intrinsic electrophysiological properties were characterized in cerebellum, further supporting a model in which the two different UBC subpopulations may have different function. In chapter 1, we investigated glutamate sensitivity and synaptic transmission from mossy fibers to UBCs in the DCN. We found that the two UBC subtypes may function as ON and OFF cells with respect to their response to glutamatergic input in a manner reminiscent of retinal bipolar cells, due to dual modes of action of glutamate and differential expression levels of glutamate receptor types in the two subtypes. mGluR1α positive UBCs had an excitatory (ON) response to glutamate, due to high expression of AMPARs and mGluR1α, and small GIRK currents elicited by mGluR2 activation. mGluR1α negative UBCs had an inhibitory (OFF) response to glutamate resulting from small AMPAR-mediated currents and large outward K+ currents activated by mGluR2. Thus, UBC subtypes may provide distinct parallel processing of multisensory input to v their target granule cells. Additionally, UBCs fire spontaneously, and this activity is critical for the ON and OFF responses. Chapter 2 describes a role of glutamate receptors in maintaining intrinsic firing of UBCs in response to a standing current generated by background levels of glutamate. I discovered that this action of glutamate is specific to UBCs as opposed to other cell types. Thus, antagonizing glutamate receptors interferes with the background firing frequency of UBCs. Furthermore, my data suggests that the origin of the glutamate mediating this standing current is vesicular.

Identifier

doi:10.6083/M4CC0ZD0

Division

Neuroscience Graduate Program

School

School of Medicine

Available for download on Friday, March 09, 2018

Share

COinS