Mirror neurons and microRNA: theory vs biological facts

Mirror neurons through the lens of epigenetics to be published in Trends in Cognitive Sciences Volume 17, Issue 9, September 2013, Pages 450–457. epub on 14 August 2013

Abstract excerpt: … we propose a new evolutionary developmental biology (evo-devo) perspective, which predicts that environmental differences early in development should produce variations in mirror neuron response patterns, tuning them to the social environment.

See Figure 1:

Excerpt: “…the early social experience produces modifications in gene expression through epigenetic marks, such as DNA methylation, histone modifications, and micro-RNA production.”

Excerpt 2: “The end result of these epigenetic modifications is the facilitation during the perinatal period, through yet unknown cellular and molecular modifications, of the canalization in the construction of the underlying neuronal circuits and the related developmental trajectories. Thus, the brain on the right would be, at birth, better tuned to respond to a set of social stimuli (e.g., facial expressions).”

See Figure 2:

Excerpt: “A consequence of these changes is that mirror neurons will be produced that, in different individuals, might result in differential responses (here represented in terms of frequency of neuronal discharge) to the same set of visual stimuli (right hand side).”

My comment:

The authors eloquently but errantly allude to unknown cellular and molecular modifications, which are commonly known to occur in species from microbes to man when individuals are exposed to olfactory/pheromonal input but not visual stimuli. Confusion about the epigenetic effects of olfactory/pheromonal input on de novo creation of olfactory receptors is probably one of the important things to be considered in the context of associative learning (e.g. Rescorla–Wagner model or Hebbian) in the context of MNS development.

In vertebrates and invertebrates, these associations are obviously made via epigenetic effects of olfactory/pheromonal input on hormone-organized and hormone-activated behaviors. That’s probably why attempts to determine cause and effect in the context of MNS development have failed miserably. There is, for example, no comparable model for the direct effect of visual input on genes in hormone-secreting nerve cells of brain tissue that might enable findings from studies of visual input to be meaningfully interpreted.

Findings that can be meaningfully interpreted in the context of a model for development of the MNS are found in the extant literature (see for example Sex Differences and the FDA Critical Path Initiative. That ‘model’ incorporates the obvious fact that nutrition is the first requirement for life, and the fact that gonadotropin releasing hormone (GnRH) -controlled reproduction is required for survival of the species. For example, we can ‘see’ how food odors and pheromones epigenetically effect the GnRH neuronal system of vertebrates, which integrates the effects of sensory input on all other neuronal systems. And we can compare those epigenetic effects in the well-established context of hormone-organized and hormone-activated invertebrate behavior.

Invertebrate behavior is more clearly “driven” by pheromones and by odors. Vertebrate behavior is clearly driven by food odors, but in some vertebrates the role of pheromones is less clear — except when the conserved molecular mechanisms in species from microbes to man are examined for similarities. What is then revealed is nutrient-dependent pheromone-controlled adaptive evolution via ecological,social, neurogenic, and socio-cognitive niche construction exemplified in this model.

Thus, “…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. ”  — Kohl (2013)

In the context of microRNA production and modifications in gene expression through epigenetic marks, such as DNA methylation, and histone modifications, what’s left is to look at the fine tuning of neuronal system development  that facilitates MNS development in humans infant who respond with sex differences to other sensory input associated with food odors and pheromones coming from the mother. See for example: Exploring the Biological Contributions to Human Health: Does Sex Matter?

“Within a few minutes after birth, the concentration of LH in serum increases abruptly (about 10-fold) in the peripheral blood of the male newborn but not in that of the female newborn. This short-lived surge in LH release is followed by an increase in the serum testosterone level during the first 3 hours that persists for 12 hours or more. In the female neonate, LH levels do not increase, and FSH levels in both males and females are low in the first few days of neonatal life. After the fall in circulating placental steroid levels, especially estrogens, during the first few days after birth, serum FSH and LH levels increase and exhibit a pulsatile pattern with wide perturbations for several months. The FSH pulse amplitude is greater in female infants, and the FSH response to hypothalamic luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone is higher in females than males throughout childhood; LH pulses are higher in males. A sex difference in plasma FSH and LH values is also present in anorchid boys and agonadal girls less than three years old.

The high gonadotropin concentrations in infancy are associated with a transient second wave of differentiation of fetal-type Leydig cells and increased serum testosterone levels in male infants for the first 6 months or so and with elevated estradiol levels intermittently in the first 1 to 2 years of life in females. The mean FSH level is higher in females than males during the first few years of life. By approximately 6 to 8 months of age in the male and 2 to 3 years of age in the female, plasma gonadotropin levels decrease to low values until the onset of puberty. Thus, the restraint of the hypothalamic LHRH pulse generator and the suppression of pulsatile LHRH secretion (and thus FSH and LH release) attain the prepubertal level of quiescence in late infancy or early childhood and earlier in boys than in girls (for reviews see Grumbach and Styne [1998] and Grumbach and Gluckman [1994]).”

In this series of events that enable postnatal sexual differentiation of the brain and behavior, the mother’s face need not be recognized by congenitally blind infants or children with autism spectrum disorder anymore than the face of another animal would need to be recognized to ensure its nutrient-dependent survival. Human infants need only somehow respond hormonally to olfactory/pheromonal input, and the development of the brain and behavior will proceed, which includes abnormal development of the MNS in sighted male infants more often than in sighted female infants. It is a mistake, however, to think that visual input is driving the development of the MNS, and especially in the context of sex differences. There’s no model for that!

Therefore, it is a mistake to think “… mirror neurons will be produced that, in different individuals, might result in differential responses (here represented in terms of frequency of neuronal discharge) to the same set of visual stimuli (right hand side).” — unless the association is first made with olfactory/pheromonal input, hormone-organization, and hormone-activation of behavior.

See also from the same issue: The chemical bases of human sociality Pages 427-429 Gün R. Semin, Jasper H.B. de Groot and see Human pheromones: integrating neuroendocrinology and ethology (2001)

Previous blog post on mirror neurons: Timing is key in the proper wiring of the brain: study

Author: James Kohl

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