Target-Dependent Release of a Presynaptic Neuropeptide Regulates the Formation and Maturation of Specific Synapses inAplysia

Abstract

The correct wiring of neurons is critical for the normal functioning of the nervous system. Sensory neurons of Aplysia form synapses with specific postsynaptic targets. Interaction with appropriate target cells in culture induces a significant increase in axon growth, the number of sensory neuron varicosities with release sites contacting the target, and regulates the expression and distribution of mRNAs encoding presynaptic proteins such as syntaxin and the sensory neuron-specific neuropeptide sensorin. Synapse stabilization is accompanied by the maintenance of presynaptic varicosities and target-dependent regulation of mRNA distributions. We report here that specific targets induce the release of sensorin from sensory neurons, which then regulates synaptic efficacy, axonal growth associated with synapse formation, the maintenance of synaptic contacts, and the specific distribution of mRNAs. Bath application of an antisensorin antibody during the early phase of synapse formation blocked the expected increase in synaptic strength, the growth and formation of new presynaptic varicosities, and the target-dependent regulation of mRNA distribution. In contrast, bath application of sensorin accelerated the increase in synaptic strength and enhanced the formation of new varicosities and target-dependent regulation of mRNA distribution in sensory neurons. As synapses stabilize, sensorin secretion declines but is required for the maintenance of synaptic efficacy, presynaptic varicosities, and mRNA distributions. These results suggest that a retrograde target signal regulates the secretion and actions of a presynaptic neuropeptide critical for the formation and maintenance of specific synapses.

Protein Kinase C Regulates Local Synthesis and Secretion of a Neuropeptide Required for Activity-Dependent Long-Term Synaptic Plasticity

“…This increase parallels that found by who found that strong paired stimulation, repeated tetani applied to isolated sensory neurons in the presence of 5-HT, also activated type 1 PKC . The absence of a significant change in sensorin expression in isolated sensory neurons with a single pairing or the smaller increase with PDBu compared with cocultures could arise from a reduction in sensorin mRNA levels at distal sites (Hu et al, 2002;Lyles et al, 2006) and a reduction in the levels of the 5-HT receptors at distal sites that lead to the activation of the appropriate PKC isoform after a single tetanus plus 5-HT Schacher, 1996, 1998;Hu et al, 2002Hu et al, , 2004b. In addition, activity plus 5-HT might regulate a retrograde signal from the target cell L7 that contributes to the changes in sensorin expression in the sensory neuron.…”

Multifunctional Role of Protein Kinase C in Regulating the Formation and Maturation of Specific Synapses

“…Sensory neurons were isolated from ganglia dissected from adult animals (80 -100 g); motor cell L7 and L11 were isolated from juvenile (1-3 g) ganglia and maintained in coculture for up to 42 h as described previously (Rayport and Schacher, 1986;Schacher et al, 1999;Hu et al, 2004b). In most cases, both targets were plated in the same culture dish, and one sensory neuron was plated with each motor neuron target.…”

“…After 24 h in culture, sensorin release into the bath is detected when sensory neurons are cultured with L7 but not with L11 (Hu et al, 2004b), and the release of sensorin at that time is required for the continued increase in synaptic efficacy, axon growth, and the formation of varicosities by sensory neurons contacting L7 (Hu et al, 2004b). Actions of sensorin contribute little to axon growth of sensory neurons cultured alone or with L11.…”

“…1, see insets). This increase in sensorin expression may contribute significantly to the targetdependent increase in sensorin secretion critical for synapse maturation and maintenance (Hu et al, 2004b) (and see below).…”

“…When contacting L7, sensory neurons extend exuberant axon growth and form numerous varicosities with transmitter release sites compared with growth by sensory neurons contacting L11, which does not induce synapse formation by sensory neurons (Glanzman et al, 1989;Schacher and Montarolo, 1991;Hatada et al, 1999;Kim et al, 2003). Target-induced secretion of sensorin, the sensory neuron-specific neuropeptide (Brunet et al, 1991), contributes to axon growth and maturation of synapses with L7 (Hu et al, 2004b). Sensorin also acts as a neurotrophin-like mol-ecule when mature sensory neuron synapses express long-term facilitation (LTF).…”