Command neuron for a half-center oscillator

Our latest paper just came out in the Journal of Neuroscience.

Command or obey? Homologous neurons differ in hierarchical position for the generation of homologous behaviors
Akira Sakurai and Paul S. Katz 
J Neurosci 17 June 2019, 3229-18
DOI: https://doi.org/10.1523/JNEUROSCI.3229-18.2019

Click here for the reprint

Nudibranchs have homologous neurons that can be identified across species. Cross-species comparisons of motor system organization provide fundamental insights into their function and origin. This paper shows that an identified cerebral ganglion neuron serves as a command neuron for the swimming behavior in a nudibranch species. The same neuron serves as a member of a central pattern generator (CPG) in another species. We described the synaptic and neuromodulatory mechanisms by which the command neuron initiates and accelerates rhythmic motor patterns.


Two sea slug species show homologous swimming behaviors
In motor systems, higher-level components issue commands that are carried out by lower-level circuits. In this paper, we describe the physiological actions of an identified neuron, which turned out to be a "command" neuron for the swimming behavior of a giant sea slug, Dendronotus iris. We determined which functional components of the swim CPG are modulated by the command inputs to initiate, maintain, and terminate the rhythmic activity of a central pattern generator circuit.

Among the swimming nudibranchs, two species Melibe leonina and Dendronotus iris show the homologous swimming behavior by flexing their bodies from left to right (Sakurai et al., 2011).
 



Homologous behaviors are produced by homologous neurons
Phylogenetic analysis indicates that the most recent common ancestor of these species likely swam in this manner, making the swimming behaviors homologous (Goodheart et al., 2015; Sakurai and Katz, 2017).

The brains of Melibe leonina (left) 
and Dendronotus iris (right)

Homologous behaviors are produced by distinct neural circuit designs
The neural circuits underlying their behaviors have been studied extensively in both species. All neurons in the swim CPGs have been identified, and their synaptic connections have been determined with careful pairwise electrophysiological recordings (Sakurai et al., 2014; Sakurai and Katz 2016). The two swim CPGs employ different network architectures for producing similar rhythmic motor patterns.

The swim CPGs of Melibe (left) and Dendronotus (right)
have distinct synaptic organizations 

Si1 as a command neuron in Dendronotus
In this study we found that Si1 neurons in Dendronotus iris serves as a neuromodulatory "command" neuron for the swim CPG.

We further revealed how such command actions were mediated by performing dynamic clamp experiments and electrophysiological manipulations.

Providing artificial synaptic boost of the Si3-to-Si2 synapse and tonic synaptic excitation of Si3 mimicked the command actions of Si1 neurons.


Synaptic and neuromodulatory actions underlie the command input
It turned out that the organization of the Dendronotus swim CPG closely resembles the model that was originally proposed for a half-center oscillator with excitatory drive arising from a command neuron (Friesen, 1994).

A classical model of the half-center oscillator (left) 
and the Dendronotus swim CPG (right)

The command neuron Si1 provides not only the overall excitatory drive but also the neuromodulation of synaptic potentiation within each half of the oscillator. Our results also suggest that the functional position of neurons in a motor hierarchy can shift from one level (CPG) to another (a command neuron) over evolutionary time.

• Friesen WO (1994) Reciprocal inhibition: a mechanism underlying oscillatory animal movements. Neuroscience and biobehavioral reviews 18:547-553.
• Goodheart JA, Bazinet AL, Collins AG, Cummings MP (2015) Relationships within Cladobranchia (Gastropoda: Nudibranchia) based on RNA-Seq data: an initial investigation. R Soc Open Sci 2:150196. 
• Sakurai A, Katz PS (2016) The central pattern generator underlying swimming in Dendronotus iris: a simple half-center network oscillator with a twist. J Neurophysiol 116:1728-1742.
• Sakurai A, Katz PS (2017) Artificial Synaptic Rewiring Demonstrates that Distinct Neural Circuit Configurations Underlie Homologous Behaviors. Curr Biol 27:1721-1734 e1723.
• Sakurai A, Newcomb JM, Lillvis JL, Katz PS (2011) Different roles for homologous interneurons in species exhibiting similar rhythmic behaviors. Curr Biol 21:1036-1043.
• Sakurai A, Gunaratne CA, Katz PS (2014) Two interconnected kernels of reciprocally inhibitory interneurons underlie alternating left-right swim motor pattern generation in the mollusc Melibe leonina. J Neurophysiol 112:1317-1328. 

Journal club: Development of the nervous system in Solenogastres (Mollusca) reveals putative ancestral spiralian features

Redl et al. EvoDevo 2014 5:48
DOI: 10.1186/2041-9139-5-48

Background: The evolutionary emergence of the Mollusca is unclear.  Some have proposed that molluscs stem from unsegmented organisms, while others say they stem from a segmented annelid-like ancestor. 

   In this study, the authors investigated the development of the nervous system in two species of solenogasters to describe the larval nervous system and also to test the hypotheses on segmented or unsegmented ancestry of molluscs. 

Observations: During the embryonic development, first neurons appear at the apical and abapical pole; the flask-shaped cells of the apical organ and the large cells associated with the suprarectal commissure are lost.

   The neuropile beneath the apical organ develops into the cerebral commissure. The cellular posterior connection of the lateral neurite bundles becomes the suprarectal commissure.

   Interestingly early nervous system development in the polychaetes shows strong similarity to the mode of neural development described here for solenogasters. They both develop apical organ with flask-shaped cells, and a single pair of longitudinal neurite bundles. Similarity in the pattern of serotonin-like immunoreactivity, and formation of the CNS from anterior and posterior ends. 

Conclusions: This study supports a nonsegmented ancestry of molluscs, but there is similarities between solenogasters and polychaetes during early nervous system development, such as the formation of the nervous system from an apical and abapical neurogenic domain.
   The authors suggest that they share neural features descent from the last common ancestor, which had no segmentation.  Segmentation may have evolved only along the line leading to the annelids.

Journal club: Evolution of highly diverse forms of behavior in molluscs

Current Biology 26, R965-71 (2016)
Binyamin Hochner and David L. Glanzman
DOI: http://dx.doi.org/10.1016/j.cub.2016.08.047

This short review paper starts off with the comparative anatomy of the nervous system.  The authors discuss the diversity of the nervous system and its co-evolution with body plan by showing a variety of nervous systems from Solenogastres to cephalopods. Then, cellular mechanisms of synaptic plasticity underlying learning in the gastropod Aplysia and the cephalopod Octopus were discussed.

The first part was fun to read.
Comparative anatomy of the nervous system is a good reminder that the molluscan nervous system, or the medullary cord, is organized in a ladder-like fashion. The loss of collinear pattern of gene expression may explain their simple body plans. The supremacy of Octopus in the motor and cognitive abilities can be due to the high expansion of two developmentally important gene families, extensive transposable element activity, and genome rearrangements.

The second part was somewhat boring.
The title says the diversity of behavior, but this part actually covers just synaptic plasticity in Aplysia (serotonin-mediated long-term facilitation) and Octopus (long-term potentiation). The mechanisms underlying the serotonergic enhancement of synaptic strength has already been described five hundred times elsewhere.  Plus, I don't think this is a valid comparison to discuss about the evolutional process, because the gill-withdrawal reflex and the higher-order learning are completely different brain functions. Such comparison merely shows different types of learning regardless of species, not actually explains the species-dependent differences or the evolution. This is like comparing the spinal reflex and motor learning in two different vertebrate species. No wonder they are different; synaptic plasticity has little to do with the diversity of behavioral expressions.