, 2005 and Crair et al., 1998). Despite this initial developmental progress, long-term dark-rearing is not benign and eventually

leads to the decline of these response properties. Remarkably, BDNF overexpression is able to prevent these detrimental effects of dark-rearing (Gianfranceschi et al., 2003). The ability of BDNF overexpression to substitute for normal sensory experience has been proposed to reflect the acceleration of GABAergic circuit maturation downstream of BDNF signaling (Hanover et al., 1999 and Huang et al., 1999). Our experiments offer an alternative role for BDNF Angiogenesis inhibitor in the control of circuit development. We found that robust sensory stimulation led to the delayed upregulation of BDNF protein, resulting in a facilitation of both synaptic LTP and LTD. Under this condition of bidirectionally elevated synaptic plasticity, experience-dependent direction selectivity training, as well as experience-expectant visual

acuity refinement, was readily enhanced. Interestingly, we observed a preferential effect on OFF stimuli. This result implies that BDNF preferentially modulated a specific subset of functional synaptic inputs in this case, and argues against it having exerted its action via nonspecific, homeostatic mechanisms or a general enhancement of GABAergic transmission. Our use of CsF in the intracellular recording solution to block GABAergic currents in recordings of visually evoked responses, as well as our having restricted SB203580 cost analysis of LTP and LTD to the short-latency responses evoked by direct optic chiasm stimulation, allow us to conclude that the improved visual acuity observed in conditioned animals was likely attributable to a BDNF-mediated facilitation of plasticity at retinotectal synapses. Nonetheless, when making measurements in a complex functional circuit it is difficult to fully exclude possible contributions of local interneurons to the changes in visual processing, especially in the these case where the improvements in visual acuity took place during a period of natural visual input. Recent evidence in Xenopus

demonstrates that the instructive contribution of plasticity mechanisms to visual field refinement depends on GABAergic inputs ( Richards et al., 2010), which themselves undergo concurrent refinement during development ( Tao and Poo, 2005). In addition, spike-timing-dependent plasticity of recurrent excitatory inputs also may play an important role in altering how neurons change their responses to visual stimuli over time ( Pratt et al., 2008). All of these components could potentially be influenced by changes in tectal levels of BDNF in response to recent visual experience. What might be the benefit of the several hour delay between the conditioning stimulus and the elevation in BDNF expression levels? Given that BDNF expression bidirectionally facilitates ongoing experience-expectant developmental plasticity, it may serve as a kind of “gain control,” setting the kinetics of baseline circuit refinement.