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Jorge
Golowasch, PhD Mailing address:
My research Regulation of excitability One of the most salient properties of the nervous system is its plasticity or capacity to change. An undesirable consequence of plasticity is the potential instability of the system. In spite of being highly plastic, neurons and neural networks maintain relatively stable properties. This can be seen at all levels of complexity, all the way from single neurons to the whole behaving animal, including humans. Neurons maintain an identity while simultaneously changing and adapting to external stimuli. What are the mechanisms that allow the nervous system to retain its plasticity and be stable simultaneously? Plasticity has been studied mostly at the level of synapses, and is believed to underlie learning and memory. However, long-term plasticity also takes place at the level of the voltage-gated ionic currents that determine cellular excitability and electric activity of both neurons and neural networks. This plasticity can in principle also underlie some forms of learning and memory, as well as recovery from injury and different sorts of perturbation. Using both electrophysiological and computational tools, in my lab we study mechanisms of neuronal plasticity and homeostasis of the ionic currents that determine the excitability and electric activity of neurons and simple neural networks in the crustacean stomatogastric ganglion (STG). Two mechanisms of long-term regulation of activity appear to be at working in STG neurons and neural networks. One appears to be activity-dependent, the other appears to be mediated by long-term effects of neuromodulatory input, also known to affect network activity in rapid response to their release. We are currently characterizing these two mechanisms and their relative role in producing and maintaining a relatively constant (but modifiable) level of rhythmic activity. One surprise has been to find that neuromodulators up to now thought to have only short term effects, control the levels and inter-ionic current coordination of several ionic currents in the long term (hours). The cellular mechanisms and the functional implications of this phenomenon are unknown and is the current focus of most of the research in the lab.
The role of gap junctions in the generation of neuronal activity is a topic of great interest. In my lab and in collaboration with Dr. Farzan Nadim we are studying the role of gap junctions in the generation of activity by neurons and neuronal networks of the STG. Using computational, electrophysiological and analytical techniques we look at how gap junctional currents interact with other ionic currents expressed by the connected neurons and how these interactions depend on current flow along the intricate branches of a neuronal dendritic tree to produce electrical activity. We have discovered that dendrite diameter controls in a non-intuitive way the transmission of signals across gap junctions, and we believe this may have important consequences for network function.
Trophic factors No trophic factors that may regulate
neuronal growth and survival in Crustaceans have to date been discovered.
In the lab we are currently screening several neuropeptides known to have
short-term neurmodulatory effects for their possible involvement in trophic
regulation of dissociated adult neurons in cultured and in long term organotypical culture.
So far we have identified one peptide family with putative trophic function and
we are continuing with this screen. We plan to then study the
intracellular signaling pathways involved in these effects, as well as their
function in the adult and in development. Important discoveries made in crustaceans - Na-K ATPase was first characterized as having the properties of such an ATPase (dependence on external Na+ and internal K+, etc) by Skou (1957. Biochem. Biophys. Acta, 23: 394-401). - Na-Ca exchange system was characterized in crab nerve (Baker & Blaustein, 1968, Biochem. Biophys. Acta, 150: 167-179) at the same time as in squid axon and cardiac muscle. - Furshpan and Potter discovered of electric synapses in 1959 working with nerve fibers of the abdominal nerve cord of the crayfish (Furshpan & Potter, 1959, J. Physiol. (Lond), 145: 289-325) - The pioneering studies showing direct inhibitory synaptic transmission were performed on the crustacean neuromuscular junction (Dudel & Kuffler, 1961, J. Physiol. (Lond), 155: 543-562, Takeuchi & Takeuchi, 1967, J. Physiol. (Lond), 191: 575-590), and the crayfish stretch receptor (Kuffler & Eyzaguirre, 1955, J. Gen Physiol, 130: 326-373). - Identification of GABA as an inhibitory transmitter was done first in the crustacean neuromuscular junction by Zack Hall, John Hildebrand and Ed Kravitz in 1974 (Chemistry of Synaptic transmission, Chiron Press, Newton, MA).
Current: Michael Gray
(MS) Past Olga Khorkova (PhD)
Rodolfo
Haedo (MS)
Rosa Rodriguez (PhD) Lola
Mukhamedieva (MS) Linda Nguyen (UG) Luis F. Corrêa (UG) John Yarotsky (UG) Chris Reina (UG) Bob LoMauro (lab tech) |
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Associate
Professor
