Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices

Abstract

Work in this laboratory demonstrated a role for rapid eye movement sleep (REMS) in critical period (CP), postnatal days (P) 17–30, synaptic plasticity in visual cortex. Studies in adolescent rats showed that REMS deprivation (REMSD) reinitiates a developmentally regulated form of synaptic plasticity that otherwise is observed only in CP animals. Subsequent work added that REMSD affects inhibitory mechanisms that are thought to be involved in terminating the CP. Neurotrophins are implicated in the synaptic plasticity that underlies CP maturation and also final closure of the CP in visual cortex. Expression of brain-derived neurotrophic factor (BDNF) is dependent upon neuronal activity, and REMSD may block BDNF expression. We propose that REMS contributes to the maturation of visual cortex through regulation of BDNF expression and consequent, downstream increase in cortical inhibitory tone. In this study, osmotic minipumps delivered BDNF into visual cortex on one side of brain. The opposite hemisphere was not implanted and served as an internal control. We tested the hypothesis that BDNF is blocked by REMSD in late-adolescent rats and investigated whether replacing BDNF prevents induction of LTPWM-III by theta burst stimulation (TBS). We also assessed relative inhibitory tone in visual cortex with paired-pulse stimulation (PPS) in animals that were similarly REMSD- and BDNF-infused. After REMSD, both hemispheres were prepared in parallel for in vitro synaptic plasticity studies (LTPWM-III or PPS). In visual cortex of REMSD rats on the side receiving BDNF infusions (8 of 8 animals), TBS consistently failed to induce LTPWM-III. In contrast, LTPWM-III was obtained (5 of 5 animals) in the matched, non-infused hemisphere, as expected in rats of this age. REMSD animals that were unilaterally infused with saline produced LTPWM-III in both hemispheres. PPS studies in another group of REMSD animals that were unilaterally BDNF-infused displayed age-appropriate inhibition of the second response on the BDNF-infused side (5/5), whereas on the non-infused side facilitation was observed (3/3). Intracortical infusion of BDNF in REMSD adolescent rats appears to restore neurochemical processes necessary for termination of the CP for developmentally regulated synaptic plasticity in visual cortex. The results suggest that REMSD blocks BDNF expression and also maturation of inhibitory processes in adolescent visual cortex. These data support REMS’ function in brain development.