Amine Modulation of I_h in a Small Neural Network

Abstract

We studied the functional role and modulation of the hyperpolarization-activated inward current (I(h)) in the pyloric network of the lobster stomatogastric ganglion. In isolated neurons, I(h) is a small current with a hyperpolarized voltage of half-activation (V(Act)) and a slow time constant of activation (tau(Act)). Bath application of dopamine (DA), octopamine (OCT), or serotonin (5HT) modified I(h) in selected synaptically isolated pyloric neurons. DA significantly enhanced I(h) in the anterior burster (AB) neuron by depolarizing its V(Act), accelerating its tau(Act), and enhancing its maximal conductance (g(max)). DA more weakly enhanced I(h) in the pyloric constrictor (PY) and ventricular dilator (VD) neurons. OCT weakly depolarized V(Act) and accelerated tau(Act) in the VD and inferior cardiac (IC) neurons. 5HT depolarized V(Act) in the IC neuron. Under control conditions with intact modulatory inputs from other ganglia, the pyloric rhythm cycles strongly at about 1-2 Hz. Bath application of the I(h) blocker cesium (Cs(+)) caused a mean increase in the period of 8%, although this effect was highly variable. When Cs(+) was applied to an isolated ganglion where the pyloric rhythm had been activated only by DA, the cycle period was consistently increased by 13.5%, with no other strong changes in rhythm parameters. These results suggest that I(h) regulates the pyloric rhythm by accelerating AB pacemaker frequency, but that this effect can vary with the modulatory conditions.

Serotonin Transduction Cascades Mediate Variable Changes in Pyloric Network Cycle Frequency in Response to the Same Modulatory Challenge

“…Considering only studies in which modulators were bath applied to deafferented preparations, one observes a large literature reporting reproducible effects of modulators on isolated ionic currents (e.g., Kloppenburg et al 2000;Peck et al 2001Peck et al , 2006Swensen and Marder 2000). These results are not inconsistent with our findings.…”

A modeling comparison of projection neuron- and neuromodulator-elicited oscillations in a central pattern generating network

“…In particular, because in this system I h is selectively blocked by bath application of Cs + (Peck et al, 2006), disruption of the PK-elicited rhythm in Cs + would strongly support the I h -dependent mechanism. Yet, due to a lack of specific blockers for I Proc and low-threshold Ca 2+ currents in this system, alternative techniques such as voltage-clamp measurements are necessary to check for any PK-induced voltage-gated ionic currents as proposed in the other two mechanisms.…”

Octopamine promotes rhythmicity but not synchrony in a bilateral pair of bursting motor neurons in the feeding circuit of Aplysia

“…Moreover, like OA, DA increased the slowly developing depolarization observed during hyperpolarizing pulses in B67 and augmented the PIR that followed such hyperpolarizing pulses (Serrano and Miller, 2006). This common constellation of effects between OA and DA may result from shared or convergent second messenger pathways, a common design of motor network modulation (Swenson and Marder, 2000;Swenson and Marder, 2001;Peck et al, 2006). Convergent actions of modulators have been well documented in neuromuscular elements of the Aplysia feeding system (Brezina et al, 1994;Brezina et al, 1995).…”

“…Hyperpolarization-activated inward currents (I h ) contribute to oscillatory activity in numerous motor systems (e.g. Arbas and Calabrese, 1987;Angstadt and Calabrese, 1989;Golowasch and Marder, 1992;Thoby-Brisson et al, 2000), and their modulation by biogenic amines can regulate rhythmic motor patterns (Kiehn and Harris-Warrick, 1992;Kjaerulff and Kiehn, 2001;Peck et al, 2006). In mollusks, the presence of an I h -like current was demonstrated in a specific motor neuron (B4) of the Lymnaea feeding network (Straub and Benjamin, 2001) (but see Vehovszky et al, 2005).…”