Journal Club: Fast Silencing Reveals a Lost Role for Reciprocal Inhibition in Locomotion

By Peter R. Moult, Glen A. Cottrell, and Wen-Chang Li
Neuron Volume 77, Issue 1, 9 January 2013, Pages 129-140

Reciprocal inhibition is considered as a fundamental building block in neural circuits for rhythmic motor pattern generation. Despite commonality in many rhythmic systems, however, the reciprocal inhibition is often found to be not a necessary component for rhythmogenesis. This is because a network is often capable of exhibiting rhythmic activity even when the reciprocal inhibition was removed mechanically or pharmacologically. The excitatory synaptic components within each half of the network are more crucial.  In this study, Wen-Chang Li's group challenged this idea by using optogenetics to hyperpolarize the entire population of neurons in one side of the spinal cord in a tadpole.

When the entire half of the spinal cord was suppressed by flashing yellow light, the other half also stopped bursting. This indicates that, in this reciprocally inhibitory network, the excitation in one side is necessary for the excitation of the other. Firing in one side would cause a bombardment of IPSPs, which induce post-inhibitory rebound. The authors also get a similar result by giving a strong hyperpolarizing current into one of the reciprocally inhibitory neurons. They concluded that the reciprocal inhibition is necessary in the tadpole swim circuit; it induces rebound excitation in the contralateral neurons.

In this paper, it is noteworthy that the author also mentioned about the "functional homeostasis" of the neural circuit. They said the rhythmic activity recovers after half an hour by itself without the reciprocal inhibition. The mechanism of the recovery still unknown.

The recovery paper has come out

Finally, my "recovery paper" came out:

Recruitment of polysynaptic connections underlies functional recovery of a neural circuit after lesion.

Akira Sakurai, Arianna N. Tamvacakis, Paul S. Katz

DOI: 10.1523/ENEURO.0056-16.2016

This paper shows that, when a neural circuit failed by losing one of its synapses within, functional recovery can occur through reorganization of the remaining neural circuitry. We show that a molluscan neural circuit recruits additional neurons in response to a lesion. The extent of recruitment predicts the extent of behavioral recovery. 

Even in a well-defined (sort of) invertebrate neural circuit, there are indirect, polysynaptic pathways that provide compensatory function or flexibility to the circuit. Such individual variability appears to be hidden under normal conditions but becomes relevant when challenged by neural injury.

This paper is a sequel of two preceding papers:

Functional Recovery after Lesion of a Central Pattern Generator (2009)

Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury (2014)

Aplysia brasiliana

Charuni, a grad student in our lab, is now studying the swimming behavior of a sea hare, Aplysia brasiliana. Compared to other sea slugs, this one looks very intelligent. Especially when they are swimming. Peeping over the water, flipping over, making quick turns... They are not sluggish at all. Their playful behaviors make me even think like these creatures are almost as intelligent as dolphins.

Dendronotus swim movie

OK, this is another nudibranch, Dendronotus iris.



Just like Melibe, it swims by lateral body flexions.

Swimming Melibe leonina

Melibe leonina swimming in a glass tank.



Shooting a movie is tough!
To make this, I spent 2 days in the tank room and 2 nights on computer.

Thompson and Watson (2005) Melibe swim paper

Sint1 cell bodies are located on the medial dorsal surface just caudal to the prominent tentacular lobe that rises from the center of the pleural ganglion. 30-50 micron.
Sint1 branches in the pleural ganglion neuropil near the base of the optic lobe and projects to the ipsilateral pedal ganglion via the dorsal pleuralpedal connective, where it forms a series of arborizations.

A single sint2 is found near the dorsal midline of each pedal ganglion.
LY staining shows that sint2 branches in the pedal ganglion neuropil and sends a major process to the opposite pedal
ganglion via the circumesophageal, pedal-pedal connective.

sint1 can cause phase advance/delay.
There is reciprocal inhibition between left and right sint1 neurons, via direct IPSP.
sint1 innervates motoneurons.
sint1 and sint2 are electrically coupled.
Mutual inhibition between sint2 neurons.
Mutual inhibition between sint2 and the contralateral sint1

Activity in Sint1 and Sint2 dissociates during other locomotor behaviors.
the CPG for swimming is formed dynamically, when activity in the sint1 and sint2 cell pairs becomes bound together. When this does not occur, the same interneurons appear to function independently during the performance of other behaviors that involve the same or similar musculature, such as turning.