Differential Modulation of Synaptic Strength and Timing Regulate Synaptic Efficacy in a Motor Network

Abstract

Neuromodulators modify network output by altering neuronal firing properties and synaptic strength at multiple sites; however, the functional importance of each site is often unclear. We determined the importance of monoamine modulation of a single synapse for regulation of network cycle frequency in the oscillatory pyloric network of the lobster. The pacemaker kernel of the pyloric network receives only one chemical synaptic feedback, an inhibitory synapse from the lateral pyloric (LP) neuron to the pyloric dilator (PD) neurons, which can limit cycle frequency. We measured the effects of dopamine (DA), octopamine (Oct), and serotonin (5HT) on the strength of the LP→PD synapse and the ability of the modified synapse to regulate pyloric cycle frequency. DA and Oct strengthened, whereas 5HT weakened, LP→PD inhibition. Surprisingly, the DA-strengthened LP→PD synapse lost its ability to slow the pyloric oscillations, whereas the 5HT-weakened LP→PD synapse gained a greater influence on the oscillations. These results are explained by monoamine modulation of factors that determine the firing phase of the LP neuron in each cycle. DA acts via multiple mechanisms to phase-advance the LP neuron into the pacemaker's refractory period, where the strengthened synapse has little effect. In contrast, 5HT phase-delays LP activity into a region of greater pacemaker sensitivity to LP synaptic input. Only Oct enhanced LP regulation of cycle period simply by enhancing LP→PD synaptic strength. These results show that modulation of the strength and timing of a synaptic input can differentially affect the synapse's efficacy in the network.

Neuromodulation of neurons and synapses

“…Multiple modulators can act on the same synapse to modify its strength, presumably depending on the behavioral need [24,25]. Such effects can be drastic: 5-HT can functionally silence synapses in the crustacean stomatogastric ganglion (STG), whereas dopamine can unmask synapses that are normally silent [26].…”

Tonic Nanomolar Dopamine Enables an Activity-Dependent Phase Recovery Mechanism That Persistently Alters the Maximal Conductance of the Hyperpolarization-Activated Current in a Rhythmically Active Neuron

“…A 10 min bath application of 100 M DA phase advanced LP, reduced LP burst duration and increased pacemaker cycle frequency (Flamm and Harris-Warrick, 1986a). Under these conditions the phase of LP was shifted relative to pacemaker kernel, and LP synaptic inhibition was ineffective because it occurred when the pacemaker kernel was in the refractory period of its oscillation (Johnson et al, 2011). LP lost its functionality in this situation; it could no longer slow cycle frequency, so the upper limit on network cycle frequency vanished.…”

“…LP may retune its resonance frequency to match the pacemaker to maintain network functionality, as the efficacy of LP feedback inhibition depends on pacemaker phase (Thirumalai et al, 2006). Indeed, LP cannot establish an upper limit on network cycle frequency in prolonged micromolar DA, because the phase relationship between LP and the pacemaker is distorted, causing LP synaptic inhibition onto the pacemaker to occur when the pacemaker is less sensitive to inhibition (Johnson et al, 2011). Alternatively changes in LP I h may alter the strength of the PD synapse onto LP.…”

“…Thus, LP firing phase determines its function within the network. It was previously shown that a 10 min exposure to micromolar DA disrupted normal LP function by distorting the phase relationship between LP and the pacemaker (Johnson et al, 2011). In contrast, population studies demonstrated that phase relationships were largely invariant between individuals and over their lifetimes (Bucher et al, 2005).…”

Patterns of Presynaptic Activity and Synaptic Strength Interact to Produce Motor Output

“…Invertebrate preparations, with their simple and accessible nervous systems, provide several useful models for the analysis of motor neuron coordination (Marder and Bucher, 2007; Goaillard et al, 2009; Buschges et al, 2011; Johnson et al, 2011). We used the leech heartbeat CPG to assess the relative contributions of temporal pattern and synaptic strength profiles in the functional coordination of motor neurons.…”