RT Journal Article SR Electronic T1 Transsynaptic Activity-Dependent Regulation of Axon Branching and Neurotrophin Expression In Vivo JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 12708 OP 12715 DO 10.1523/JNEUROSCI.2172-11.2011 VO 31 IS 36 A1 Anda-Alexandra Calinescu A1 Tiecheng Liu A1 Michael M. Wang A1 Jimo Borjigin YR 2011 UL http://www.jneurosci.org/content/31/36/12708.abstract AB The two major classes of activity-dependent neuroplasticity predict different consequences of activity alteration on circuit response. Hebbian plasticity (positive feedback) posits that alteration of neuronal activity causes a parallel response within a circuit. In contrast, homeostatic plasticity (negative feedback) predicts that altering neuronal activity results in compensatory responses within a circuit. The relative roles of these modes of plasticity in vivo are unclear, since neuronal circuits are difficult to manipulate in the intact organism. In this study, we tested the in vivo effects of activity deprivation in the superior cervical ganglion–pineal circuit of adult rats, which can be noninvasively silenced by exposing animals to constant light. We demonstrated that total deprivation of sympathetic activity markedly decreased the presence of axonal proteins in the pineal and reduced the density and thickness of sympathetic axonal arbors. In addition, we demonstrated that sympathetic inactivity eliminated pineal function and markedly decreased pineal expression of neurotrophins. Administration of β-adrenergic agonist restored the expression of presynaptic and postsynaptic proteins. Furthermore, compensatory axonal growth through collateral sprouting, normally seen following unilateral denervation of the pineal, was profoundly impaired in the absence of neural activity. Thus, these data suggest that sympathetic axonal terminals are maintained by neural activity that induces neurotrophins, which may act through a retrograde mechanism to preserve the integrity of axonal arbors via a positive feedback loop. Conversely, by using Hebbian-like neuroplasticity, silent yet intact circuits enter a hibernation mode marked by reduction of presynaptic axonal structures and dramatically reduced postsynaptic expression of neurotrophins.