Research Topics
We are interested in the principles of organization of neuronal circuits in the auditory brainstem. Various anatomical and physiological techniques are employed to uncover the structure and function of nuclei of the superior olive in order to better understand their roles in hearing. Immunocytochemical techniques reveal the neurotransmitters used by specific populations of cells, and tract-tracing methods uncover their synaptic targets and source of inputs. This type of work is performed at both the light and electron microscopic levels.
Neurons of the SPON display a distinct multipolar morphology and strongly express the inhibitory neurotransmitter GABA. Numerous GABAergic synaptic terminals are apposed to the soma and dendrites of this cell.
In our electrophysiology lab, we perform
in vivo extracellular recordings of sound-evoked activity in brainstem neurons, and selectively block receptors for inhibitory neurotransmitters to uncover the role of inhibition in shaping their response properties.
Examples of sound-evoked spike activity records from neurons of the MNTB and SPON. The sound stimulus presentation is depicted by the horizontal bar. MNTB units fire is a sustained fashion during the stimulus and display spontaneous activity, but SPON units only discharge at the stimulus offset.
Our work addresses the principles of organization of particular neuronal microcircuits and utilizes anatomical and cytological techniques, with emphasis on characteristic chemical phenotypes that can be revealed with immunocytochemistry. The research is centered on a pair of nuclei in the mammalian auditory brainstem, the MNTB and the SPON. To reveal the synaptic connectivity of these cell groups, we use brain microinjections of substances that are subsequently transported via physiological transport mechanisms. Both light and electron microscopy are used to analyze these sorts of data, as the resolution required to identify a synaptic contact unequivocally is only achieved at the ultrastructural level.
Electron micrograph of a neuronal dendrite that has been pre-labeled by immunocyto-chemistry using antiserum to a calcium binding protein. Arrows denote synaptic contacts between axons and spines of this dendrite. Electron dense synaptic junctions and synaptic vesicles can be seen.
We also perform
in vivo extracellular recordings of sound-evoked activity in single auditory neurons. These recordings are designed to test functional hypotheses about the roles of various brainstem centers in hearing. Application of drugs that selectively block receptors for GABA and glycine are also applied, reversibly, to identify the specific roles of these inhibitory neurotransmitters in shaping the response properties of the cell population under study.
Peri-stimulus time histograms showing the change in spike activity of an auditory neuron under control conditions and when its receptors for GABA and glycine are blocked by application of bicuculline and strychnine (middle trace). After the drugs wash out, the baseline activity pattern is recovered. The vertical light blue lines depict the time window during which the cell is presented with its best frequency tone stimulus.
Our long term goal is to develop a better understanding of neural mechanisms underlying hearing, and thereby contribute to the development of refined prosthetic devices to assist the hearing impaired.