Molluscan Memory of Injury: Evolutionary Insights into Chronic Pain

 Brain Behav Evol 2009; 74: 206-218

DOI: 10.1159/000258667

Edgar T. Walters and Leonid L. Moroz

In this paper, the authors raise an interesting hypothesis that the plasticity mechanisms underlying learning and memory in higher organisms may have evolved from adaptive responses that repair damaged neuronal processes or body parts. Persistent nociceptive sensitization in Aplysia nervous system displays many functional similarities to alterations in mammalian nociceptors associated with the clinical problem of chronic pain. The original responses induced regrowth of damaged axon, increased excitability, enhanced release of transmitter, and reorganization of cellular network. Such compensatory responses would be critical for survival in the early age.

Before discussing about the origin of chronic pain and synaptic plasticity, the authors also described how great Aplysia is. They compared molluscs with other model systems like arthropod and nematode by comparing the number of gene homologues that are shared by mammals, and their evolutionary distances from mammals. Mollucs are closer to mammals because they split earlier. Slower rate of gene evolution provided molluscs more homologous genes associated with human disease than Drosophila or C. elegans. DNA methylation can also be seen in molluscs. Thus, integration of genomics and physiological studies in molluscan neurons offers a powerful comparative approach to address molecular and cellular aspects of selected neurological problems.

Altogether, molluscan preparations should become increasingly useful for comparative studies across phyla that can provide insight into cellular functions of clinically important genes.

Review: New genes from old: asymmetric divergence of gene duplicates and the evolution of development

Holland PW, Marlétaz F, Maeso I, Dunwell TL, Paps J. 2017

Phil. Trans. R. Soc. B 372: 20150480.

http://dx.doi.org/10.1098/rstb.2015.0480

Genome or genes sometimes get duplicated just partially within a single cell even when it is not dividing. The gene duplication and divergence provide a critical source of genetic novelty during evolution. This review paper discusses the fates of duplicated homeobox genes, focusing on asymmetric divergence after gene duplication. Duplicated genes differentiate independently (or asymmetrically) to different degrees. They often become key genes of new functions.
   One of the copied genes can mutate and sometimes acquires a new function, while the others may lose their function. Overall number of genes changes as a result of total duplication-modification and deletions. Repetition of this process over millions of years result in a whole family of genes in a single genome. Duplicate copies often change asymmetrically to have different functions. Their expression becomes different in time and loci. This is how orthologs and paralogs were made.

This review provides examples are Hox genes in Lepidoptera, TALE-class genes in molluscs, extra PRD-class genes in placental mammas.  Tapeworms have lost around one-third of all homeobox genes generally present in bilaterian animals. The evolution of the globulin gene family shows how DNA duplications contribute to the evolution of organisms (Molecular Biology of the Cell, pp461).

Production of redundant copies and repurposing them for other functions sounds similar to the neural circuit evolution.  It seems like evolution is all about repurposing of given resources to create new functions. 

Review: Vertebrate brains and evolutionary connectomics: on the origins of the mammalian 'neocortex'

Phil. Trans. R. Soc. B 370: 20150060.  (2015)
http://dx.doi.org/10.1098/rstb.2015.0060

by Harvey J. Karten

This review paper covers not just the history of studies on avian brain which dates back to the Darwin era, but it also tells the story of the author's long quest for the answer of how laminar structure of mammalian neocortex was developed and it had diverged from the nuclear structures of avian brain.

   Mammalian brain and avian brain are very different in forebrain organization. The mammalian brain has laminated cortex structure. In contrast, the avian brain has nuclear clusters that are interconnected. Despite such differences, both animals can perform complex cognitive behaviors, such as sensory perception, decision making, and language capability.
   Recent studies have suggested homology in the molecular features of neurons and the structures of microcircuits (Wang et al., 2010). This "nucleus to layer" hypothesis was further supported by Dugus-Ford et al. (2012) showing that each of the distinct nuclei of the avian telencephalon also expressed various genetic molecular features that very closely match those of layers of the mammalian neocortex to which they were speculatively linked. Such homology can track back to fish. Calabrese and Woolley (2015) demonstrated that the avian auditory pallium exhibits the same information-processing principles that define the canonical cortical microcircuit, which is similar to the lamina-specific properties of mammalian cortex. They provided a physiological explanation for the evolution of neural processes that give rise to complex behavior in both mammals and birds.
  The author has also stated several times in this paper that the microcircuit structure that is commonly seen in vertebrate brains may have originated from the age that is older than the ancestoral reptile of avian and mammals. It is fun to imagine how birds and mammals employed microcircuit as a common building block to built their own brains.

Overall, the paper was mostly written in plain English and it was fun to read. 

Journal club: Phylogenic plasticity of crustacean stomatogastric circuits

by Pierre Meyrand and Maurice Moulins

J. exp. Biol. 138, 107-132, 133-153 (1988)

This old twin papers describe a neural network that has a very similar designs to that of related species but produces distinct patterns of output. They concluded that the differences in the pattern of motor output depend more on the action of the extrinsic neuromodulation onto individual neurons than the synaptic architecture of the network.

I. Pyloric patterns and pyloric circuit of the shrimp Palaemon serratus
http://jeb.biologists.org/content/138/1/107

To find the general rules of neural circuit function, direct comparison of different circuits may be useful. Finding a common principle or 'building blocks' may help understanding the fundamental mechanisms underlying rhythmic pattern generation. In this study, the authors investigated the stomatogastric nervous system of a shrimp and compared it with those of larger crustaceans such as lobster and crab. They found that pyloric networks are very similar between this shrimp and large crustaceans.

The pattern of their rhythmic outputs are quite different.  In large decapods, the pyrolic circuit generate triphasic rhythm. The pacemaker AB fire in antiphase with the constrictor motoneurones (LP and PY). In shrimp, AB fires in phase with the constrictor neurones because of electrical connection; endogenous oscillatory property was only found in LP.

II. Pyloric patterns and pyloric circuit of the shrimp Palaemon serratus

http://jeb.biologists.org/content/138/1/133

The previous study (above) showed that the fundamental network architectures are almost identical between large decapods and the shrimp. This study investigate how extrinsic modulatory inputs contribut to produce the motor outputs of different patterns.

They found that the shrimp neurons responded differently to muscarinic agonist and dopamin than those in large decapods. For example, oxotremorine activated PY, while dopamine activated PD. In large decapods, muscarinic agnonist causes oscillation in PDs while inhibit PDs. In shrimp, AB neuron is driven by and returns an inhibitory feedback to the commissural pyrolic oscillator. In large decapods, AB is the conditional oscillator and act as the pacemaker.

   Altogether, the phylogenetic plasticity in motor pattern production does not derive from structural differences in the corresponding central neuronal circuits themselves. Rather it is due to the difference in the modulatory system controlling these circuits. 

Journal club: Recent Clione papers

Arshavsky published a series of studies on the Clione swim CPG. Those papers are "must read" for researchers who work on CPG. I pay the highest respect to them.They were published in late 80's and now can be categorized as classical papers.
   More recently, there came a series of papers performing more detailed(?) analyses on this system. The following are my impressions with regard to those recent Clione papers.

2004
"Cellular mechanisms underlying swim acceleration in the pteropod mollusk Clione limacina"
by Pirtle and Satterlie
Integr. Comp. Biol. (2004) 44 (1): 37-46. doi: 10.1093/icb/44.1.37

Clione can swim faster when attacking a prey. It had been suggested that 5-HT mediates the acceleration of the swim motor pattern. In this study, the authors examined what membrane current components were modified by 5-HT.
   It seems to me that the experiments were not well designed. The way they compared the effects of drugs seems problematic (e.g., Fig. 7D). Figures were not well arranged. A control swim activity was not presented in Fig. 2 but then shown in Fig. 3. The authors called ion channel blockers as "antagonists." Antagonists are for receptors. No description of what neurons they used. The introduction was great, though.


2006
"The contribution of the pleural type 12 interneuron to swim acceleration in Clione limacina"
by Pirtle and Satterlie
Invert Neurosci (2006) 6:161–168. DOI 10.1007/s10158-006-0029-8

In this paper, the authors examined the role of type-12 neurons in the swim acceleration.
   Type-12 neuron is recruited into the type7/8 half-center network when the CPG gets into the fast swim mode. Arshavsky et al. (1985) suggested that this neuron plays an important role in the swim acceleration by rewiring the circuit. It turned out that activation of type-12 had only a transient effect on the swim cycle frequency. They suggested that type 12 has rather minor roles in maintaining the fast swim mode. Its function may be bilateral coordination or to increase the stability of the network. Despite negative results, this paper is more interesting than the other two.


2010
"A hyperpolarization-activated inward current alters swim frequency of the pteropod mollusk Clione limacina"
Pirtle, Willingham, and Satterlie
Comparative Biochemistry and Physiology, Part A 157 (2010) 319–327. DOI:10.1016/j.cbpa.2010.07.025

I don't see much difference between this and the previous 2004 paper. The only change was that they now show ZD7288 data instead of CsCl. In Fig. 5E. They stated ZD7288 blocked the 5-HT effect. I cannot agree with that. If compared with Fig. 4D data, I see that 5-HT still increases the swim cycle frequency even in the presence of ZD7288. Oh and again they were still calling ZD7288 as an "antagonist" for Ih current.

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.