Tapping into the vocal learning and rhythmic synchronization hypothesis

Theofanopoulou BMC Neuroscience (2024) 25:63 https://doi.org/10.1186/s12868-024-00863-2 BMC Neuroscience Open Access CO M M E N T Tapping into the vocal learning and rhythmic synchronization hypothesis Constantina Theofanopoulou1,2,3* Abstract In this article, I present three main points that could benefit the “vocal learning and rhythmic synchronization hypothesis”, encompassing neurogenetic mechanisms of gene expression transmission and single motor neuron function, classification of different behavioral motor phenotypes (e.g., spontaneous vs. voluntary), and other evolutionary considerations (i.e., the involvement of reward mechanisms). Keywords Vocal learning, Rhythmic synchronization, Rhythm entrainment, Beat synchronization, Language, Speech, Dance The “vocal learning and rhythmic synchronization hypothesis” (VLRSH) [1], formulated by Ani Patel, aims to explain how the evolution of advanced vocal learning in humans and parrots may have resulted in their ability to synchronize nonvocal movements to a rhythmic beat. I believe this hypothesis provides one of the most promising avenues for linking the evolution of two core components (i.e., vocal learning and rhythmic synchronization) that are necessary for complex sensorimotor behaviors such as speech, song, and dance. Earlier versions of this hypothesis [2, 3] have been influential in shaping my research agenda, where I currently focus on studying the brain pathways involved in speech and dance production and learning in humans. In this version of the VLRSH [1], Patel delves deeper into the neurobiological mechanisms, proposing that the evolution of a strong integration between auditory regions and vocal dorsal premotor This comment refers to the article available online at https://doi. org/10.1186/s12868-024-00843-6. *Correspondence: Constantina Theofanopoulou 1 Rockefeller University, New York, NY, USA 2 Center for Ballet and the Arts, New York University, New York, NY, USA 3 Drexel University, Philadelphia, PA, USA regions in ancestral humans (via the laryngeal pitch control pathway) involved gene regulation changes which fortuitously enhanced the strength of neural connections between auditory and nonvocal dorsal premotor regions near the vocal dorsal premotor regions. Ani Patel has invested significant effort in synthesizing existing literature to construct a hypothesis that is both robust and testable. While acknowledging the solidity of Patel’s work that has uniquely inspired my research, I identify areas within the hypothesis that merit further refinement and exploration. In this commentary, I intend to address three specific points derived from Patel’s hypothesis. Firstly, I will dig into the neural mechanisms and suggest an alternative or complementary scenario for the gene regulation changes in neighboring brain regions that, according to Patel [1], could have led to the enhancement of the brain pathways needed for rhythmic synchronization. Secondly, I advocate for a more profound understanding of what constitutes “voluntary”, “involuntary”, “reflexive” or “spontaneous” movements, whether vocal or nonvocal, as a beneficial addition to the hypothesis. Thirdly, I will present my perspective on an additional parameter that Patel suggests could have contributed to the human and parrot ability to dance: their © The Author(s) 2024. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Theofanopoulou BMC Neuroscience (2024) 25:63 “craving for social interaction and a strong sensitivity to social reward [4]”. Adjacent and/or overlapping motor circuits for vocal learning and rhythm synchronization One of the fundamental tenets of the VLRSH is the notion that gene regulation changes in specific neurons, particularly those engaged in the integration between auditory and vocal dorsal premotor regions, triggered alterations in the gene regulation of adjacent or nearby neurons involved in the integration between auditory and nonvocal dorsal premotor regions. However, the mechanistic details of how neurons can directly impact the gene expression of neighboring neurons remain unclear. While certain mechanisms exist, such as neurotransmitter signaling influencing the electrical activity of the receiving neuron, the release of neurotrophic factors from one neuron to another, or activity-dependent plasticity, none of these mechanisms explain the proposed “infection” of gene expression to adjacent neurons posited by the VLRSH. While formulating my working hypothesis for studying in tandem the speech and dance brain pathways in humans, I was able to find only limited instances of research demonstrating the feasibility of gene expression transmission from one neuron to another. For instance, experiments involving Xenopus tectal neurons revealed that overexpressing Candidate Plasticity Gene 15 (CPG15) not only enhanced dendritic outgrowth and synapse maturation in the directly overexpressed neurons but also influenced these characteristics in adjacent neurons, potentially through intercellular interactions [5, 6]. Another set of experiments in transgenic animal models of neurodegenerative diseases also identified the “spread” of gene expression properties in neighboring neurons [7]: in these models, the accumulation of Tau in neurons expressing a transgene resulted in tau aggregates developing in adjacent neurons lacking the transgene but receiving projections from transgene-expressing neurons, possibly through a trans-synaptic prion-like mechanism [7]. Additionally, in neuropathic pain mouse models, experimental injury to a set of neurons in the dorsal root ganglion led to differential gene regulation in the injured neurons also affecting gene regulation in nearby intact neurons, possibly through the activation of intracellular second messenger systems inducing immediate early genes (IEGs) controlling expression changes in other genes [8]. While these studies offer insights into potential mechanisms for studying the VLRSH, (...truncated)