Site-Specific and Sensory Neuron-Dependent Increases in Postsynaptic Glutamate Sensitivity Accompany Serotonin-Induced Long-Term Facilitation atAplysiaSensorimotor Synapses

Abstract

Long-term changes in the efficacy of Aplysia sensory neuron (SN) connections accompany behavioral training or applications with 5-HT. The changes evoked by training or 5-HT include formation of new SN varicosities and transmitter release sites. Because new synapse formation requires proper alignment of presynaptic structures with postsynaptic zones containing a high density of transmitter receptors, we examined whether changes in postsynaptic sensitivity to the presumed SN transmitter (glutamate) were correlated with formation and distribution of new SN varicosities in contact with motor cell L7 in cell culture. The formation of stable SN connections after 4 d in culture did not significantly change overall responses to focal applications of glutamate. However, specific sites along L7's axon apposed to SN varicosities expressed larger responses to glutamate compared with adjacent sites with few SN varicosities. After treatments with 5-HT that evoked long-term changes in both the structure and the function of SN-L7 synaptic interaction, glutamate responses increased selectively at sites along the surface of L7's axon with preexisting or new SN varicosities. Increases in postsynaptic response to glutamate 24 hr after 5-HT treatment required interaction with an SN. These results suggest that new synapse formation between neurons, either with regeneration or after external stimuli that evoke increases in synaptic efficacy, involves site-specific changes in expression of functional neurotransmitter receptors on the postsynaptic cell that is regulated by interaction with the presynaptic neuron.

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

“…Such transmitters and neuropeptides are known to function during development, where they can regulate neuronal survival, differentiation and maturation, [108][109][110] as well as synaptic plasticity. 111,112 Taken together, we suggest that these data support a model in which cognitive and emotional impairments of schizophrenic patients are caused by two fundamental alterations; persistent qualitative (structural/phenotypic) neural changes that occurred during development, and impaired synaptic plasticity caused by quantitative and qualitative changes in neurotransmitter systems. Both sets of changes can be mediated by altered cytokines and growth factors, interacting with environmental influences.…”

Serotonin facilitates AMPA‐type responses in isolated siphon motor neurons of Aplysia in culture

“…Possibly, the sensitivity to DNQX of glutamate receptors in solitary motor neurons differs from that of postsynaptic glutamate receptors in sensorimotor co-cultures. This idea receives support from a recent study by Zhu et al (1997). These investigators found a difference in the ability of glutamate receptors in Aplysia motor neurons to undergo a 5-HT-induced increase in sensitivity that depended upon whether or not the glutamate receptors were opposed, or near to, presynaptic varicosities.…”

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

“…Axonal growth, varicosity formation, and increases in synaptic efficacy are all blocked when the actions of sensorin are blocked by exogenous anti-sensorin Ab. Previous studies (Glanzman et al, 1989(Glanzman et al, , 1990Bailey et al, 1992;Bank and Schacher, 1992;Zhu et al, 1997;Casadio et al, 1999;Hatada et al, 1999;Kim et al, 2003) indicate that the formation of varicosities on the major processes of L7 is a consequence of neuritic growth, includes the formation of new release sites, and increases in synaptic efficacy. However, modulation of sensorin levels has little influence on axon extension by sensory neurons growing alone.…”