Areas of Interest
- Prefrontal and somatosensory cortex
- Pyramidal neurons
- Synaptic transmission
- Excitatory neurotransmitters
- The role of dendrites in synaptic integration
- Dopaminergic modulation of dendritic excitability
Lab Rotation Projects
Project Description: Dopamine is synthesized in neurons whose
cell bodies are located in the brain stem. One group of
dopamine-producing neurons (ventral tegmental area) sends their
long axons to the prefrontal cortex (Figure 1). Electron
microscope studies in monkey and human clearly demonstrate that
dopamine synaptic contacts onto cortical neurons are located
almost exclusively on the distal dendrites and spines of distal
dendrites (Figure 2). What is the functional significance of
glutamate-dopamine ultrastructural juxtaposition? Why is it
necessary to have a dopamine release site right next to the
glutamate release site, on the same dendritic spine? Is dopamine
involved in the precise control of the excitatory glutamatergic
synapse?
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Figure 1. Mesocortical dopaminergic pathway. Dopaminergic projection from the ventral tegmental area (red) to the prefrontal cortex (blue) is implicated in
the control of mood, motivation and reward. |
Figure 2. Glutamate-dopamine interaction. Gluamatergic (black and dopaminergic (red) axon terminals impinge onto the same dendritic spine in the prefrontal
cortex. |
The level of prefrontal cortex dopamine is critical for
modulating normal cognitive/behavioral processes. One important
hypothesis is that deviations from the critical levels can
severely disrupt cognitive processes and result in mental
disorders such as schizophrenia. At present, it is not known how
dopamine interacts with prefrontal cortex neural circuits.
We are using in vitro experimental methods to study how
dopamine affects glutamate-evoked dendritic membrane potentials.
Distal dendritic regions of thin dendrites, where the
interaction between glutamatergic and dopaminergic signals
actually takes place, are difficult to probe with glass
electrodes. In order to measure directly the dendritic response
to glutamatergic excitation we use optical recording techniques.
Optical methods adopted in our laboratory are based on
intracellularly applied calcium-sensitive and voltage-sensitive
dyes (Figure 3).
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Figure 3. Dendritic imaging. Simultaneous whole-cell (channel 0) and fast multi-site voltage-sensitive dye recordings from the dendritic tree (channels 1-17). A doublet of action
potentials was evoked by direct current injection in the soma (modified from Antic, 2003). |
Selected Publications
Acker CD and Antic SD (2009) Quantitative assessment of the
distributions of membrane conductances involved in action
potential backpropagation along Basal dendrites J Neurophysiol.
101(3):1524-41.
Moore AR, Filipovic R, Mo Z, Rasband MN, Zecevic N, Antic SD
(2008) Electrical Excitability of Early Neurons in the Human
Cerebral Cortex during the Second Trimester of Gestation. Cereb
Cortex. Nov 17. [Epub ahead of print].
Antic SD, Acker CD, Zhou WL, Moore AR (2008) Dopaminergic
modulation of dendritic excitability in neocortical pyramidal
neurons. Cellscience Reviews, Vol 5 No 2. ISSN 1742-8130.
Antic SD, Acker CD, Zhou WL, Moore AR and Milojkovic BA (2008)
The role of dendrites in the maintenance of UP state. In:
Mechanisms of spontaneous active states in neocortex. Ed.
Timofeev I. Research Signpost, Kerala India.
Zhou WL, Yan P, Wuskell JP, Loew LM and Antic SD (2008) Dynamics
of action potential backpropagation in basal dendrites of
prefrontal cortical pyramidal neurons. European Journal of
Neuroscience. (4):923-36.
Milojkovic BA, Zhou WL and Antic SD (2007) Voltage and calcium
transients in basal dendrites of the rat prefrontal cortex.
Journal of Physiology. 585(Pt 2):447-68.
Milojkovic B, Radojicic M, and Antic SD (2005) A strict
correlation between dendritic and somatic plateau
depolarizations in the rat prefrontal cortex pyramidal neurons.
Journal of Neuroscience 25(15):3940-51.
Milojkovic BA, Wuskell JP, Loew L, and Antic SD (2005)
Initiation of sodium spikelets in basal dendrites of neocortical
pyramidal neurons. Journal of Membrane Biology 209(2): 155-169.
Milojkovic B, Radojicic M, Goldman-Rakic P and Antic SD (2004)
Burst generation in rat pyramidal neurones by regenerative
potentials elicited in a restricted part of the basilar
dendritic tree. Journal of Physiology 558(1): 193-211.
Rev. 3/09 |
