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.
- Neurobiology of hearing and deafness.
- Neuroscience Study Abroad Program.
The general goal of our lab is to understand how information
about sound is processed by the brain. The inferior colliculus
(IC) is at the center of the auditory pathway. 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.
Publications
Selected Publications
Malmierca MS, Izquierdo MA, Cristaudo S, Hernández O,
Pérez-González D, Covey E, Oliver DL (2008) A discontinuous
tonotopic organization in the inferior colliculus of the rat. J
Neurosci. 28: 4767-4776.
http://dx.doi.org/doi:10.1523/JNEUROSCI.0238-08.2008.
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
154: 196-205.
http://dx.doi.org/doi:10.1016/j.neuroscience.2008.01.019.
Altschuler RA, Tong L, Holt AG, Oliver DL (2008)
Immunolocalization of Vesicular Glutamate Transporters 1 and 2
in the Rat Inferior Colliculus. Neuroscience 154: 226-232.
http://dx.doi.org/doi:10.1016/j.neuroscience.2008.03.036.
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.
 View more publications, see
Pubmed listing. Revised
September, 2008. |
