Exploring the Effects of BDNF in Populations and Neurons of the Adult Cortical Primary Somatosensory Cortex
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is an important signaling molecule that plays a crucial role in the proper development and function of the central nervous system. A variety of studies have suggested BDNF meets the criteria necessary to modulate cortical reorganization, including a study that found its transcription and release to be activity-dependent. Horizontal synapses in the primary somatosensory area, S1, facilitate functional reorganization across topographical representations. However, the molecular contributors to reorganization are not known. Since BDNF is a known modulator of synaptic transmission, this dissertation focuses on the effects of BDNF on horizontal synapses in S1, hypothesizing that BDNF has the capacity to alter synaptic transmission at these synapses.
In chapter 1, we found that acute bath application of BDNF had an inhibitory effect on layer II/III local field potentials. The inhibitory effect of BDNF was found to be Trk dependent, as inhibiting protein kinase activity proved to prevent BDNF-dependent inhibition. The mechanism of inhibition shown by BDNF is likely to be similar to a long- term depression (LTD) -like mechanism, because inducing LTD prior to BDNF exposure occluded the BDNF effect, and BDNF exposure prior to LTD induction occluded the LTD effect. The LTD that occluded the BDNF effect was shown to be non-N-methyl-D- aspartic acid receptor (NMDAR) dependent, as it was unaffected by application of an NMDAR antagonist.
In chapter 2, we continued to investigate the inhibitory effect of BDNF by exploring the mechanism by which the LFP was reduced. Using a whole-cell patch clamp technique, we found that BDNF reduces the excitatory post synaptic current, EPSC, of both NCB and CB populations without changing the inhibitory post synaptic current, ISPC. BDNF was also found to reduce excitability by significantly increasing rheobase, the amount of current required to elicit a single action potential. Stimulating trains of action potentials resulted in BDNF-exposed cells having a reduction in the amount of action potentials they produced. All together, these findings support BDNF acting to inhibit excitation in these populations of cells. This inhibition by BDNF could be necessary in supporting the synaptic plasticity that is prompted during reorganization.