The goal of research in our laboratory is to understand signal transmission in the nervous system with particular emphasis on mechanisms that control synaptic transmission under normal and pathological conditions. Two projects at present involve electrophysiological recordings from neurons of the hippocampus, an area critically involved in learning and memory. One project is focused on the properties of neuronal voltage-gated calcium channels; the other is on rapid modulation of synaptic strength by neurotrophins.
Neuronal voltage-gated calcium channels provide a pathway for calcium influx that is required for processes ranging form intracellular signaling to alterations in cellular excitability. In hippocampal neurons, we have found that a subtype of dihydrophridine-sensitive calcium channel shows multiple kinds of voltage-dependent potentiation of its activity. One type of potentiation appears to be unique to central neurons; it has a low threshold and survives transient hyperpolarization. A second type is elicited by much higher voltages and is selectively deactivated at hyperpolarized voltages. Thus, as with synaptic transmission, calcium channel plasticity in the hippocampus has a variety of forms distinguished by their stimulus requirements and duration.
Neurotrophins are important regulators of the survival, development, and differentiation of multiple neuronal populations. These effects generally occur over the course of hours, or even days. Recently, evidence has accumulated that neurotrophins can also modulate synaptic transmission. In the hippocampus, we have found that brain-derived neurotrophic factor (BDNF) rapidly and reversibly enhances the strength of synaptic connections. Both the amplitude and the frequency of excitatory post-synaptic currents are increased within two to three minutes of neurotrophin application. Moreover, the potentiation of synaptic current amplitude occurs via a novel post-synaptic mechanism in which BDNF increases the responsiveness to excitatory input. These results suggest a central role for this neurotrophin in the modulation of synaptic transmission in the hippocampus.
