Melanie K. Tallent , Ph.D.
Assisitant Professor
Ph.D. (1995) University of Pennsylvania
Phone: 215-762-8208
Email: melanie.tallent@drexelmed.edu
The major research focus of our laboratory is in the regulation of neurotransmission by neuropeptides in normal and diseased brain. We use a variety of in vitro electrophysiological techniques, combined with transgenic animals and pharmacological approaches, to understand basic brain function and relevance to disease. One important aspect of this research is examining the role of neuropeptides in epilepsy and temporal lobe seizures. Several recent studies in animal models of epilepsy and transgenic mice point to neuropeptides as important endogenous antiepileptics. Our goal is to understand the cellular mechanisms through which inhibitory neuropeptides cause a reduction in seizure activity, using electrophysiological techniques in hippocampus, neocortical and amygdala slices. We also study the role of peptides in normal brain processes, such as learning and memory (Fig. 1).
Figure 1. Long-term potentiation (LTP) is a cellular model of learning and memory in which application of high frequency trains to inputs (yellow arrow) causes a long-lasting potentiation of the synaptic response. In mice that overexpress the neuropeptide cortistatin (CST) in the dentate gyrus region of the hippocampus (CST tgs), the ability to evoke LTP is lost. These findings are confirmed by our studies which showed exogenous application of CST blocks the induction of LTP. Interestingly, learning deficits are also found in these mice, supporting our findings that the cellular processes associated with learning are impaired in these mice.
Another research interest is the role of the M-current in regulating neuronal activity. One mechanism through which inhibitory neuropeptides depress excitation in hippocampus is through increasing the M-current. This voltage-sensitive K+ current is critical in setting the receptivity of a neuron to synaptic input. Channel subunits that underlie the M-current are mutated in a human neonatal epilepsy and other diseases. We are therefore characterizing the developmental regulation of these K+ channels and their involvement in seizures (Fig. 2) in hippocampus and neocortex both at the molecular and functional level. These studies should provide insight into the ontogeny of neonatal and other epilepsies.
Figure 2. Blocking the M-current with the selective antagonist linopirdine causes a transition from brief interictal (“non-seizure”) bursts to sustained ictal (“seizure”) bursts. Extracellular recording from CA3 region of rat hippocampal slice.
We are also interested in understanding how drugs of abuse lead to long-term alterations in brain function. Neuropeptides such as neuropeptide Y and CRF appear to play a critical role in some neuroadaptations associated with drug use. We are examining the role of peptides in brain regions and circuitry critical in addiction, such as the central nucleus of the amygdala. For example, we are interested in whether long-term exposure to alcohol or narcotics alters the cellular actions of neuropeptide Y in central amygdala neurons, as suggested by whole animal studies. These studies should have important implications in understanding and treating drug addiction.
Selected References
Tallent, M. K. and Siggins, G. R. (1997) Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus. J. Neurophysiol. 78 (6): 3008-3016.
Tallent, M. K. and Siggins, G. R. (1999) Somatostatin acts in CA1 and CA3 to reduce hippocampal epileptiform activity. J. Neurophysiol. 81 (4): 1626-1635.
Sanna, P. P., Berton, F., Cammalleri, M., Tallent, M. K., Siggins, G. R., Bloom, F. E., and Francesconi, W. (2000) A role for Src kinase activity in spontaneous epileptiform activity in the CA3 region of hippocampus. Proc. Nat. Acad. Sci. 97: 8653-8657.
Tallent, M. K., Madamba, S. G., and Siggins, G. R. (2001) Nociceptin reduces epileptiform events in CA3 hippocampus through presynaptic and postsynaptic mechanisms. J. Neurosci. 21 (17): 6940-6948.
Baratta, M. V., Lamp, T., and Tallent, M. K. Somatostatin depresses long-term potentiation and Ca2+ signaling in mouse dentate gyrus. In press J. Neurophysiol. |