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photo of srdjan d. anticSrdjan D. Antic
Assistant Professor of Neuroscience
antic@neuron.uchc.edu

Research Interests:

  • Prefrontal and somatosensory cortex;
  • Pyramidal neurons;
  • Synaptic transmission
  • Excitatory neurotransmitters;
  • The role of dendrites in synaptic integration;
  • Dopaminergic modulation of dendritic excitability

Project Description:
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?

image of mesocortical dopaminergic pathway

image of glutamate-dopamine interaction

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).

image of dendritic imaging
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:

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, 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, 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.

Antic SD, (2003) Action potentials in basal and oblique dendrites of rat neocortical pyramidal neurons. Journal of Physiology (550(1): 35 - 50.

rev 4-08

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