Transsynaptic impulse activity regulates postsynaptic density molecules in developing and adult rat superior cervical ganglion.

Abstract

Ganglionic postsynaptic density protein (PSDp) was used to monitor the influence of transsynaptic impulse activity on synaptic structure in the developing and adult rat superior cervical sympathetic ganglion (SCG). Since transsynaptic activity is known to regulate ontogeny of postsynaptic transmitter enzymes, we initially studied the developing ganglion. Denervation in neonates prevented normal development, decreasing calmodulin binding to the ganglionic PSDp by 71% after 4 weeks. During this period, denervation elicited only a 42% decrease in total protein of the synaptic membrane fraction, suggesting that innervation regulates development of various synaptic components differentially. Effects of denervation were extremely rapid, resulting in a 44% decrease in calmodulin binding within 1 day, consistent with regulation by a signaling process such as impulse activity. The effect of impulse activity was examined more directly in adults by treatment with the agents reserpine or phenoxybenzamine, which elicit reflex increases in sympathetic transmission. Administration of reserpine resulted in a progressive 90% increase in calmodulin binding to the PSDp over 4 weeks. Phenoxybenzamine also elicited an increase, mimicking the effects of reserpine. Neither agent altered total protein of the synaptic membrane fraction, suggesting that impulse activity regulates specific synaptic components. Finally, ganglionic denervation in adults decreased PSDp binding within 12 hr, consistent with acute effects of impulse reduction. Our results suggest that transsynaptic impulse activity plays an important role in regulation of specific molecular components of the synapse.

Depolarization regulates expression of a synaptic vesicle protein in rat superior cervical ganglia in vitro

“…However, at least part of the change in p65 levels caused by deafferentation in vivo is due to the loss of neuronal activity since it can be mimicked by pharmacological blockade of preganglionic transmission in neonates and adults (Greif, 1986;Greif and Linderman, 1986 In ciliary ganglia, cholinergic agonists and antagonists appear to modulate the number of acetylcholine receptors (Smith ct al., 1986). Following dcafferentation of the SCG, an 85% decrease in calmodulin-binding to postsynaptic densities is observed (Wu and Black, 1988). Changes in p65 levels may reflcct either changes in the numbers of vesicles or changes in the number of p65 molecules associated with vesicles.…”

Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy.

“…In contrast, the 120-kDa and 110-kDa proteins were decreased but detectable in brains of mdx mice. Another marker associated with the PSDs, the major PSD protein (21)(22)(23)(24), derived from mdx brain was unaffected as judged from calmodulin binding (data not shown). The decreased expression of the 120-and 110-kDa molecular species in mdx brains was apparently specific, since equal amounts of protein were loaded on each lane, and since other species, such as the band at 70 kDa, for example, were identical in mdx and normals (Fig.…”

“…We focused on the cortical postsynaptic density (PSD), a disc-shaped proteinaceous structure attached to the inner surface of the postsynaptic membrane. The PSD appears to be central to synaptic function (20)(21)(22)(23)(24).…”

Changes in glutamate immunoreactivity in the somatic sensory cortex of adult monkeys induced by nerve cuts

“…Since the expression of neurotransmitters and neuromodulators, as well as that of postsynaptic molecular structures, is regulated in an activity-dependent manner (Hendry and Jones, 1986Nishimori et al, 1988;Wu and Black, 1988;Neve and Bear, 1989;Schoups and Black, 1991;Castren et al, 1992;Hanisch et al, 1992), changes in neurotransmitters and/or second messenger levels could conceivably be such triggering events. Indeed, the finding that in the cerebral cortex of adult rats and monkeys, levels of y-aminobutyric acid (GABA), GABA-synthesizing enzyme glutamate-decarboxylase (GAD), and GABAA receptors are regulated in an activity-dependent manner Jones, 1986, 1988a;Warren et al, 1989;Hendry et al, 1990Hendry et al, , 1994Garraghty et al, 1991; Benson et al, 1994) lead to the suggestion that activity-dependent changes in GABAergic function play a role in cortical representational plasticity (Jones, 1993).…”