Bursting emerges from the complementary roles of neurons in a four-cell network

Abstract

Rhythmically active neural circuits often contain reciprocally inhibitory modules that act as half-center oscillators. In half-center oscillators, alternating burst discharges require a mechanism to transition activity from one phase to the next, which requires particular synaptic and membrane properties. Here we found that active membrane properties of specific neurons and the temporal dynamics of particular synapses both contribute to the production of a stable rhythmic motor pattern in the swim central pattern generator (CPG) of the nudibranch mollusc, Dendronotus iris. This CPG is composed of only four neurons that are organized into two competing modules of a half-center oscillator. Each module is composed of a Swim Interneuron 2 (Si2) and the contralateral Swim Interneuron 3 (Si3). Si2 and Si3 each inhibit their own contralateral counterparts; however, the S2 contralateral synapses have a more negative reversal potential, making them more effective at hyperpolarizing the Si2 and the electrically coupled Si3 of the other module. Si3 rebounds first from inhibition due to a hyperpolarization-activated slow inward current. Si3 excites the Si2 in its module through both chemical and electrical synapses. An Si2-evoked slow inhibitory synaptic potential in Si3 suppresses its firing, terminating the burst generated by the module. Using dynamic clamping, we showed that the magnitude of the slow inhibition sets the periodicity of the oscillator. Thus, the network-driven oscillation is produced by each module rebounding from inhibition, maintaining the burst through self-excitation, and then terminating its burst through a buildup of slow synaptic inhibition, thereby releasing the other module from inhibition.

Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits

“…Moreover, these interneurons are not latent bursters either, as they do not burst even when perturbed with constant external currents [41]. Neurophysiological experiments on the swim CPGs [16][17][18][19][20][21][22][23] have demonstrated that their interneurons are either quiescent at most times, or become tonic-spiking during swim episodes when receiving excitatory drives from sensory cells. This strongly suggests that the slow bursting (of period ranging from 2 through 14 seconds, resp., in juvenile and grown animals) observed in the experimental studies on the swim CPGs in the sea slugs is indeed a network-level dynamical phenomenon emerging due to nonlinear interactions between the interneurons orchestrated by complex coordination of fast and slow currents, including synaptic ones.…”

“…In addition, there is a weak electrical synapse or a gap junction between the neurons. The gap junction was reported in the biological EI-module, which happens to be the key building block in the swim CPG of the sea slug Dendronotus iris [23]. Unlike the chemical synapses, the gap junction is bi-directional, and the corresponding current is described by an additional term I elec syn = g elec (V post − V pre ), in the voltage equation (1), where g elec ≃ 1 − 2 × 10 3 nS.…”

“…The CPG circuits underlying their behaviors have been studied extensively in both species [17][18][19][20]. All neurons in the CPGs have been identified, and their synaptic connections have been determined with careful pairwise electrophysiological recordings [21][22][23]. The swim CPGs in these sea slugs do not include endogenously bursting pacemakers.…”

Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits

“…Moreover, these interneurons are not latent bursters either, as they do not burst even when perturbed with constant external currents 40 . Neurophysiological experiments on the swim CPGs [15][16][17][18][19][20][21][22] have demonstrated that their interneurons are either quiescent at most times, or become tonic-spiking during swim episodes when receiving excitatory drives from sensory cells. This strongly suggests that the slow bursting (of period ranging from 2 through 14 sec, resp., in juvenile and grown animals) observed in the experimental studies on the swim CPGs in the sea slugs is indeed a network-level dynamical phenomenon due to nonlinear interactions between the interneurons orchestrated by complex coordination of fast and slow currents, including synaptic ones.…”

Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits

“…The CPG circuits underlying their behaviors have been studied extensively in both species [16][17][18][19] . All neurons in the CPGs have been identified, and their synaptic connections have been determined with careful pairwise electrophysiological recordings [20][21][22] . The swim CPGs in these sea slugs do not include endogenously bursting pacemakers.…”