Research Description:
Untitled Document
Neuronal circuits underpin all animal behavior. While circuit components are relatively fixed, behaviors are plastic; they can be modified over the short- and long-term, in part, because neuromodulators alter the properties of circuit elements. We are interested in the neuromodulatory signal transduction cascades that shape the integrative and response properties of neurons over multiple time scales.
Dopamine is a neuromodulator that normally regulates many central nervous system (CNS) circuits involved in motor control, cognition and affect. It is thought that abnormalities in dopaminergic neuromodulation in these CNS circuits can lead to Parkinson's disease and schizophrenia. Treatments for these diseases have involved the continued use of medications that activate (Parkinson's ) or inhibit (schizophrenia) dopaminergic signal transduction cascades in neurons. However, chronic use of these drugs evokes homeostatic plasticity in CNS circuits, which in turn, alters the expression of proteins in dopaminergic transduction cascades. These drug-induced, persistent alterations in dopaminergic transduction cascades then alter cellular properties and circuit output in an unpredictable manner, leading to complications, such as the development of tardive dyskinesia in schizophrenics. In order to design more effective therapies for these major illnesses, it is necessary to understand the molecular underpinnings of dopaminergic signal transduction.
The signal initiated by a dopminergic receptor can have multiple spatial and temporal components, each of which can differentially contribute to cell and circuit plasticity over multiple time scales. Our lab uses a variety of molecular, cellular, imaging and electrophysiological techniques to study the dopaminergic signal transduction cascades operating in indentified rhythmogenic neurons of a well-characterized circuit. The long-term goal of this work is three-fold: 1. To define the local and global elements of a dopaminergic signal. 2. To examine the contributions of the local and global components of a dopaminergic signal to the integrative and response properties of a neuron. 3. To understand how dopaminergic signaling cascades are customized in individual cells and over time in order to produce an adaptable, rhythmic output from a neuron.
Recent Publications:
Cui D, Dougherty KJ, Machacek DW, Sawchuk M, Hochman S, Baro DJ. (2006) Divergence between motoneurons: Gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons. Physiological Genomics, 24(3):276-89.
Clark, MC and DJ Baro (2006) Cloning and characterization of crustacean type one dopamine receptors: D1 aPan and D1bPan. Comparative Biochemistry and Physiology-Part B: Biochemistry and Molecular Biology, 143: 294-301.
MC Clark, TE Dever, JJ Dever, P Xu, V Rehder, MA Sosa, DJ Baro (2004) Arthropod 5-HT2 receptors: A neurohormonal receptor in Decapod crustaceans that displays agonist independent activity resulting from an evolutionary alteration of the DRY motif. The Journal of Neuroscience, 24:34213435
Sosa MA, Spitzer N, Edwards DE, Baro DJ. (2004) A crustacean serotonin receptor: Cloning and distribution in the thoracic ganglia of crayfish and freshwater prawn. Journal of Comparative Neurology 473:526-537.
Soto I, Marie B, Baro DJ, Blanco RE. (2003) FGF-2 modulates expression and distribution of GAP-43 in frog retinal ganglion cells after optic nerve injury. J Neurosci Res. 73(4):507-17
See more publications >>
Back to top
|
