State-, Timing-, and Pattern-Dependent Neuromodulation of Synaptic Strength by a Serotonergic Interneuron

Abstract

Here we report that a serotonergic neuron evokes two distinct neuromodulatory actions with different state, timing, and firing pattern dependencies. These neuromodulatory actions may have important behavioral functions. In the mollusc, Tritonia diomedea, EPSCs evoked by ventral swim interneuron B (VSI) exhibited intrinsic plasticity; after a spike train, EPSC amplitude increased from a basal state to a potentiated state, which usually lasted Ͼ10 min. While the synapse was in a potentiated state, stimulation of a serotonergic dorsal swim interneuron (DSI) decreased VSI synaptic strength, returning it to a basal state. The extent of the DSI-evoked decrement was strongly correlated with the magnitude of the homosynaptic potentiation. This synaptic reset, or depotentiation, by DSI was blocked by the serotonin receptor antagonist methysergide and mimicked by a serotonin puff. In contrast to this state-dependent neuromodulatory action, we found that a previously described DSI-evoked transient enhancement of VSI synaptic strength was state-independent, producing the same multiplicative increase in EPSC amplitude regardless of whether the synapse was in a potentiated or basal state. These two actions also differed in their dependencies on the firing pattern of DSI and VSI action potentials. Results suggest that stateindependent synaptic enhancement by DSI may play a short-term role during a swim motor pattern, whereas state-dependent actions may have longer-lasting consequences, resetting VSI synaptic strength after a swim bout. Thus, differences in two neuromodulatory actions at one synapse may allow a serotonergic neuron to play distinct roles at different stages of a motor pattern.

Beyond the wiring diagram: signalling through complex neuromodulator networks

“…In modulatory networks, more than sufficient scope for very complex nonlinearities, and so complex computations, appears to exist, for example, in the interactions between multiple modulators at the synapses where they modulate each other's release (Vizi & Lábos 1991;Stjärne & Stjärne 1995;Lundberg 1996;Salio et al 2006)-sometimes even differentially the release of just a specific subset of the total modulator complement (DeLong et al 2009)-and in their modulation, through intracellular signal-transduction pathways, of each other's receptors and so actions (Sebastião & Ribeiro 2000). Rooted in such interactions are then higher-order functional phenomena such as metamodulation (Katz & Edwards 1999;Stein 2009), the gating of the actions of one modulator by another (Dickinson et al 1997;Svensson et al 2001), complex dependence of the expression of the modulator actions on the state and activity of the underlying neuronal network (Ito & Schuman 2008;Sakurai & Katz 2009), and ultimately, it has been proposed, even such top-level functionalities of the vertebrate nervous system as the representations of memory, salience, reward, expectation and uncertainty (Hasselmo 1995;Yu & Dayan 2005;Cragg 2006). Very complex computations are inherent also in the processing of the released modulators-in particular, the purines and the neuropeptides-by the extracellular processing enzymes that transform the cocktail of active modulators into another cocktail with different activities, with dynamics that themselves can be modulated (Dale & Gilday 1996;Konkoy & Davis 1996;Dale 2002;Nusbaum 2002;Huxtable et al 2009).…”

Composite Modulatory Feedforward Loop Contributes to the Establishment of a Network State

“…Localization of neuromodulators to specific neurons made it possible to change the focus of research from studying overall actions of modulators on CPG networks to more specific studies of how neuromodulators may account for the actions of individual neurons that contain them (e.g., Harris-Warrick and Marder 1991;Jing and Weiss 2001;Jing et al 2007Jing et al -2009Koh et al 2003;Nusbaum and Beenhakker 2002;Sakurai and Katz 2009). Such studies are well illustrated by the actions of two modulatory pathways in Aplysia: one of which originates in the higher-order interneuron, CBI-3 Morgan et al 2002) and the other in the EN.…”

Gastric and pyloric motor pattern control by a modulatory projection neuron in the intact crabCancer pagurus

“…stomatogastric nervous system; central pattern generator; sensorimotor; descending control; neuromodulation ONE OF THE BIGGEST CHALLENGES today is to determine how the neuromodulatory system contributes to the neuronal plasticity that allows the nervous system to respond adequately to different behavioral tasks (Gu 2002;Calabrese 2003;Krichmar 2008;Brezina 2010). In particular, motor pattern generating circuits show a high degree of flexibility due to neuromodulatory substances that trigger new patterns or modify ongoing activity (Morgan et al 2002;Nusbaum and Beenhakker 2002;Marder et al 2005;Dickinson 2006;Sakurai and Katz 2009). Recent studies (Chen et al 2009) have addressed the complexity and variety of paracrine neuromodulator release in vivo, but much less is known about the in vivo activity of neuromodulatory neurons that control behavior.…”

“…In particular, motor pattern generating circuits show a high degree of flexibility due to neuromodulatory substances that trigger new patterns or modify ongoing activity (Morgan et al 2002;Nusbaum and Beenhakker 2002;Marder et al 2005;Dickinson 2006;Sakurai and Katz 2009). Recent studies (Chen et al 2009) have addressed the complexity and variety of paracrine neuromodulator release in vivo, but much less is known about the in vivo activity of neuromodulatory neurons that control behavior.…”