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Faculty
Douglas L. Oliver
Professor of Neuroscience
doliver@neuron.uchc.edu
Areas of Interest:
Neurobiology of Auditory System
- Structure and function of CNS sensory neurons.
- Microcircuitry and Network organization
- Ionic currents and channel expression and their role in
information processing.
- Biology of hearing and deafness.
The general goal of our lab 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. We are part of an international effort to unlock the secrets of
this part of the brain.
Current work in the lab is focused on :
(1) Studies of the synaptic organization of the inputs to IC.
(2) Studies mechanisms that control the postsynaptic neurons in the IC.
(3) Plasticity and activity dependent changes in the IC after neonatal
sound exposure.
We use many different methodologies. Neurons are studied in vivo so
that we can use sound to identify their function. Neurons are also
studied in vitro so that we can see the cell types and networks in
isolation. Most of our experiments involve some combination of
morphology, physiology, or molecular biology. Experimental methods
include binaural auditory physiology in vivo as a routine part of
anatomical experiments; whole-cell recordings in brain slices; in situ
hybridization; immunohistochemistry; histology for tract tracing and CNS
tissue. Optical methods include brightfield, darkfield, epi-fluorescence,
infrared differential interference contrast, and confocal microscopy. We
frequently use advanced image processing and 3D reconstruction tools.
Lab Rotation Projects:
Neuroscience projects that could turn into a dissertation.
- Synapses. Two basic circuits in the IC are proposed. In one, large
IC neurons receive a dense, calyx-like excitatory synaptic input on the
cell body and proximal dendrites. These synapses contain VGLUT2, a
molecule that loads the transmitter glutamate into synaptic vesicles.
The other circuit has smaller IC neurons with only VGLUT1-positive glutamatergic inputs on smaller dendrites. Circuitry in the IC is also
notable because of many inhibitory inputs from the lower auditory
brainstem. We hypothesize that inhibitory inputs from different sources
have segregated targets in the IC. To identify the components of the IC
circuitry, the excitatory and inhibitory inputs to IC will be identified
in separate experiments that combine auditory physiology and tract
tracing with in situ hybridization or immunohistochemistry.
- Neurons. To understand the two basic circuits in the IC, we must
identify the postsynaptic neurons that receive the calyx-like input as
well as the other IC neurons. Three different approaches on the same
mouse animal model will identify the neurons in the two basic IC
circuits: 1) identification of gene products related to specific ion
channels, 2) axonal targeting, and 3) neurotransmitter content. In the
first, the “molecular signatures” for IC neurons will be identified. A
battery of molecular and electrophysiological experiments will show how
the firing patterns and membrane properties of IC neurons are related to
specific types of ion channels. This process will uncover the identity
of the neurons with the VGLUT2 calyx-like glutamate input in addition to
discovering molecular signatures for all IC neurons. In the second, the
axonal target of the IC neurons with axosomatic glutamate inputs will be
studied with retrograde transport and immunohistochemistry. In the
third, transgenic mice whose GABAergic neurons are marked by GFP are
used to discover the role of GABAergic neurons in the basic circuits of
the IC. These mice also are used in the experiments above so the
molecular signatures and axonal targeting of GABAergic neurons will be
revealed. It is proposed that the two basic IC circuits use different
neuron types with different axonal targets in the auditory pathway.
- Plasticity. Sound exposure at the beginning of life may alter
hearing. In rodents and even humans, the ear is not fully developed at
birth. Because the ear is not mature at the onset of hearing, it may
take some time for the entire auditory system to become activated by
sound. We are developing experiments that explore the normal development
of sound-driven activity in the auditory system. These experiments are
motivated by our findings that sound exposure during the first week of
hearing can alter function permanently in the IC.
Students who wish to formulate their own novel questions about the
synaptic organization of the auditory system are more than welcome.
Oliver Lab Page
Publications
Selected Publications:
Loftus WC, Malmierca MS, Bishop DC , Oliver DL (2008) The
cytoarchitecture of the inferior colliculus revisited: a common
organization of the lateral cortex in rat and cat. Neuroscience, In
Press.
http://dx.doi.org/doi:10.1016/j.neuroscience.2008.01.019
Sivaramakrishnan S, Oliver DL (2006) Neuronal responses to lemniscal
stimulation in laminar brain slices of the inferior colliculus. J Assoc
Res Otolaryngol 7:1-14.
http://dx.doi.org/doi:10.1007/s10162‑005‑0017‑4
Oliver DL (2005) Neuronal organization in the inferior colliculus.
Chapter 2. In: The Inferior Colliculus (Winer JA, Schreiner CE, eds).
New York : Springer-Verlag.
Yang Y, Saint Marie RL, Oliver DL (2005) Granule cells in the
cochlear nucleus sensitive to sound activation detected by Fos protein
expression. Neuroscience 136:865-882.
http://dx.doi.org/doi:10.1016/j.neuroscience.2005.02.007
Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe
ID, Oliver DL, Kaczmarek LK (2005) Acoustic environment determines
phosphorylation state of the Kv3.1 potassium channel in auditory
neurons. Nature Neurosci 8:1335-1342.
http://www.nature.com/neuro/journal/v8/n10/pdf/nn1533.pdf
Malmierca MS, Saint Marie RL, Merchan MA, Oliver DL (2005) Laminar
inputs from dorsal cochlear nucleus and ventral cochlear nucleus to the
central nucleus of the inferior colliculus: two patterns of convergence.
Neuroscience 136:883-894.
http://dx.doi.org/doi:10.1016/j.neuroscience.2005.04.040
Sivaramakrishnan S, Sterbing-D'Angelo SJ, Filipovic B, D'Angelo WR,
Oliver DL, Kuwada S (2004) GABA(A) synapses shape neuronal responses to
sound intensity in the inferior colliculus. J Neurosci 24:5031-5043.
http://dx.doi.org/doi:10.1523/JNEUROSCI.0357%1E04.2004
Loftus WC, Bishop DC, Saint Marie RL, Oliver DL (2004) Organization
of binaural excitatory and inhibitory inputs to the inferior colliculus
from the superior olive. J Comp Neurol 472:330-344.
http://dx.doi.org/doi:10.1002/cne.20070
Oliver DL, Beckius GE, Bishop DC, Loftus WC, Batra R (2003)
Topography of interaural temporal disparity coding in projections of
medial superior olive to inferior colliculus. J Neurosci 23:7438-7449.
http://www.jneurosci.org/cgi/reprint/23/19/7438
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