Hormonal Modulation of Sensorimotor Integration

Abstract

Neuronal circuits commonly receive simultaneous inputs from descending, ascending, and hormonal systems. Thus far, however, most such inputs have been studied individually to determine their influence on a given circuit. Here, we examine the integrated action of the hormone crustacean cardioactive peptide (CCAP) and the gastropyloric receptor (GPR) proprioceptor neuron on the biphasic gastric mill (chewing) rhythm driven by the projection neuron modulatory commissural neuron 1 (MCN1) in the isolated crab stomatogastric ganglion. In control saline, GPR stimulation selectively prolongs the gastric mill retractor phase, via presynaptic inhibition of MCN1. In the absence of GPR stimulation, CCAP does not alter retraction duration and modestly prolongs protraction. Here, we show, using computational modeling and dynamic-clamp manipulations, that the presence of CCAP weakens or eliminates the GPR effect on the gastric mill rhythm. This CCAP action results from its ability to activate the same modulator-activated conductance (G MI ) as MCN1 in the gastric mill circuit neuron lateral gastric (LG). Because GPR prolongs retraction by weakening MCN1 activation of G MI in LG, the parallel G MI activation by CCAP reduces the impact of GPR regulation of this conductance. The CCAP-activated G MI thus counteracts the GPRmediated decrease in the MCN1-activated G MI in LG and reduces the GPR ability to regulate the gastric mill rhythm. Consequently, although CCAP neither changes retraction duration nor alters GPR inhibition of MCN1, its activation of a modulator-activated conductance in a pivotal downstream circuit neuron enables CCAP to weaken or eliminate sensory regulation of motor circuit output.

Functional consequences of neuropeptide and small-molecule co-transmission

“…Such regulation provides added flexibility (and uncertainty, for the experimentalist) to the microcircuit response to a co-transmitting neuronal input. Examples of this selective regulation include the impact of hormonal modulation and proprioceptor feedback to the MCN1-driven gastric mill rhythm 59,138,141,142 (FIG. 6).…”

Consequences of acute and long-term removal of neuromodulatory input on the episodic gastric rhythm of the crabCancer borealis

“…This presents an interesting challenge for understanding how excitability and responses to modulators are controlled in neurons that may only be episodically activated, sometimes with days or weeks between epochs of activity. It is generally thought that the episodic gastric rhythm is specifically activated by descending neuromodulatory neurons, triggered by specific sets of sensory inputs (Beenhakker et al 2005(Beenhakker et al , 2007Blitz et al 1999Blitz et al , 2004Combes et al 1999;Dando and Selverston 1972;DeLong and Nusbaum 2010;Nusbaum and Marder 1989a). Because the period of time between feedings may vary considerably in the wild, it is also possible that the mechanisms governing the activation of the gastric rhythm must be robust to a very intermittent activation schedule.…”

Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales

“…The single firing rate (10 Hz=100 ms inter-spike interval) and burst duration (4.8 s) used were also within the physiological range of LG activity (inter-spike interval: 50-250 ms; burst duration: 2-9 s) (Beenhakker et al, 2004(Beenhakker et al, , 2005(Beenhakker et al, , 2007Blitz et al, 2004bBlitz et al, , 2008Colton and Nusbaum, 2014;DeLong and Nusbaum, 2010;Diehl et al, 2013;Hedrich et al, 2011;Kirby and Nusbaum, 2007;White and Nusbaum, 2011). Thus, our data indicate that during gastric mill rhythms triggered by multiple inputs, augmentation and facilitation/ depression would regulate responses of the three target muscles of LG.…”

“…For instance, at the short end of the spectrum of physiological inter-burst intervals (3-4 s) (Beenhakker et al, 2004;Colton and Nusbaum, 2014;Diehl et al, 2013;Saideman et al, 2007), gm5b reached a peak depolarization with the first EJP, while gm6ab and gm8a depolarization increased over several EJPs even at 2 s. This could result in a faster rising phase of a gm5b contraction relative to the other LG innervated muscles. However, at long inter-burst intervals, such as those in response to proprioceptive feedback (∼15-25 s) (DeLong and Nusbaum, 2010), gm5b EJPs undergo facilitation instead of depression. Thus, at these longer intervals, the gm5b muscle would likely also require multiple LG action potentials to reach a peak response, and result in similar contraction onset between the three LG innervated muscles.…”

“…Diehl et al (2013) focused on distinctions in the pattern of spiking within LG bursts, but a number of other aspects of LG activity differ depending on modulatory state and the complement of inputs acting on LG. In response to a number of different modulatory inputs, LG activity consists of firing rates of 4-20 Hz (50-250 ms inter-spike intervals), burst durations of 2-8 s and interburst intervals of 2-24 s in vitro and in vivo (Beenhakker et al, 2004(Beenhakker et al, , 2005(Beenhakker et al, , 2007Blitz et al, 2004bBlitz et al, , 2008Colton and Nusbaum, 2014;DeLong and Nusbaum, 2010;Diehl et al, 2013;Hedrich et al, 2011;Kirby and Nusbaum, 2007;White and Nusbaum, 2011). Similar to central and peripheral synapses in other systems, electrical responses at neuromuscular junctions in the STNS are shaped by multiple forms of activity-dependent synaptic plasticity including depression, facilitation and augmentation (Daur et al, 2012b;Jorge-Rivera et al, 1998;Katz et al, 1993;Sen et al, 1996;Stein et al, 2006).…”