Developmental emergence of different forms of neuromodulation in Aplysia sensory neurons

Abstract

The capacity for neuromodulation and biophysical plasticity is a defining feature of most mature neuronal cell types. In several cases, modulation at the level of the individual neuron has been causally linked to changes in the functional output of a neuronal circuit and subsequent adaptive changes in the organism's behavioral responses. Understanding how such capacity for neuromodulation develops therefore may provide insights into the mechanisms both of neuronal development and learning and memory. We have examined the development of multiple forms of neuromodulation triggered by a common neurotransmitter, serotonin, in the pleural sensory neurons of Aplysia californica. We have found that multiple signaling cascades within a single neuron develop sequentially, with some being expressed only very late in development. In addition, our data suggest a model in which, within a single neuromodulatory pathway, the elements of the signaling cascade are developmentally expressed in a ''retrograde'' manner with the ionic channel that is modulated appearing early in development, functional elements in the second messenger cascade appearing later, and finally, coupling of the second messenger cascade to the serotonin receptor appearing quite late. These studies provide the characterization of the development of neuromodulation at the level of an identified cell type and offer insights into the potential roles of neuromodulatory processes in development and adult plasticity.

Serotoninergic Modulation of Chloride Homeostasis during Maturation of the Locomotor Network in Zebrafish

“…This may be because the neural network for swimming is not yet fully established, as discussed in detail by Brustein et al (2003b). In addition, it is possible that intracellular signaling mechanisms linking 5HT receptor activation and regulation of bumetanide-sensitive chloride cotransport are yet to be established (Marcus and Carew, 1998) (see below).…”

Serotonin patterns locomotor network activity in the developing zebrafish by modulating quiescent periods

“…For example, motoneurons of the zebrafish larva do not show a pronounced postspike afterhyperpolarization (Buss and Drapeau, 2001), which is a common target for 5-HT modulation in the spinal cord (reviewed by Schmidt and Jordan, 2000), and this could explain the absence of changes in swimming frequency. Furthermore, even if the appropriate channels are present, the intracellular signaling mechanisms that make them responsive to 5-HT may not yet be established (Marcus and Carew, 1998).…”

Developmental Changes in Eye-Blink Conditioning and Neuronal Activity in the Inferior Olive

“…Much is known regarding the developmental changes in the neurophysiological mechanisms of learning in Aplysia californica (Carew, 1989;Marcus and Carew, 1998), but there have been few neurophysiological studies of learning in developing mammals (Freeman and Nicholson, 2000). Most of what is known about the time course of mammalian developmental changes in learning and neural function comes from correlations between the ontogeny of particular learned responses and the progression of anatomical maturation of the neural systems underlying these learned responses in adults (Green and Stanton, 1989;Diamond, 1990; Freeman and Stanton, 1991;Rudy, 1992;Stanton et al, 1992;Hunt and Campbell, 1997;Stanton, 2000).…”