TY - JOUR T1 - Limited Recovery of Pineal Function after Regeneration of Preganglionic Sympathetic Axons: Evidence for Loss of Ganglionic Synaptic Specificity JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4867 LP - 4874 DO - 10.1523/JNEUROSCI.3829-12.2013 VL - 33 IS - 11 AU - Jaisri R. Lingappa AU - Richard E. Zigmond Y1 - 2013/03/13 UR - http://www.jneurosci.org/content/33/11/4867.abstract N2 - The cervical sympathetic trunks (CSTs) contain axons of preganglionic neurons that innervate the superior cervical ganglia (SCGs). Because regeneration of CST fibers can be extensive and can reestablish certain specific patterns of SCG connections, restoration of end organ function would be expected. This expectation was examined with respect to the pineal gland, an organ innervated by the two SCGs. The activity of pineal serotonin N-acetyltransferase (NAT) exhibits a large circadian rhythm that is dependent on the sympathetic input of the gland, with high activity at night. Thirty-six hours after the CSTs were crushed bilaterally, nocturnal NAT was decreased by 99%. Three months later, enzyme activity had recovered only to 15% of control values, a recovery dependent on regeneration of CST fibers. Nevertheless, a small day/night rhythm was present in lesioned animals. Neither the density of the adrenergic innervation of the gland nor the ability of an adrenergic agonist to stimulate NAT activity was reduced in rats with regenerated CSTs. In addition, stimulation of the regenerated CST at a variety of frequencies was at least as effective in increasing NAT activity as seen with control nerves. These data suggest that the failure of pineal function to recover is not attributable to a quantitative deficit in the extent of reinnervation or synaptic efficacy. Rather, we suggest that there is some loss of specificity in the synaptic connections made in the SCG during reinnervation, resulting in a loss of the central neuronal information necessary for directing a normal NAT rhythm and thus normal pineal function. ER -