Autopoiesis, Thermodynamics, and the Natural Drift of Living Beings: Another Way to the New Evolutionary Synthesis.

The New Evolutionary Synthesis (NES) groups a series of theories that, departing from the gene-centric approach of Modern Synthesis evolutionary theory (MS), place the organism as the central agent of evolution. Two versions of NES, each one with advantages and disadvantages, can be distinguished in this regard; the restrictive NES and the comprehensive NES. Comparatively, the comprehensive NES is a more robust theoretical construction than the restrictive one because it comes grounded on a general, thermodynamically informed theory of living beings (something that the restrictive NES lacks). However, due to its strong teleological commitments, the comprehensive NES has serious problems fitting with modern science's methodological framework; a problem that the restrictive version, with no explicit commitment to teleology, does not face. In this paper, we propose the autopoietic approach to evolution as a way of integrating these two versions of NES, combining the theoretical robustness of the comprehensive view with the methodological appropriateness of the restrictive one. The autopoietic approach, we show, offers a non-teleological, organism-centered theory of evolution, namely the natural drift theory (NDT), and a grounding on a thermodynamic theory of living beings, namely the embodied autopoietic theory (EAT). We conclude that, from the programmatic point of view, an autopoietic (NDT plus EAT) approach to evolution offers a promising way to develop the NES project.

Maintained Spatial Learning and Memory Functions in Middle-Aged α9 Nicotinic Receptor Subunit Knock-Out Mice.

Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.

Physiological Evidence for Delayed Age-related Hearing Loss in Two Long-lived Rodent Species (Peromyscus leucopus and P. californicus).

Deer mice (genus Peromyscus) are an emerging model for aging studies due to their longevity relative to rodents of similar size. Although Peromyscus species are well-represented in genetic, developmental, and behavioral studies, relatively few studies have investigated auditory sensitivity in this genus. Given the potential utility of Peromyscus for investigations of age-related changes to auditory function, we recorded auditory brainstem responses (ABRs) in two Peromyscus species, P. californicus, and P. leucopus, across the lifespan. We compared hearing sensitivity and ABR wave metrics measured in these species with measurements from Mus musculus (CBA/CaJ strain) to assess age-related effects on hearing across species. Recordings in young animals showed that all species had similar hearing ranges and thresholds with peak sensitivity ranging from 8 to 16 kHz; however, P. californicus and P. leucopus were more sensitive to frequencies below 8 kHz. Although M. musculus showed significant threshold shifts across a broad range of frequencies beginning at middle age and worsening among old individuals, older Peromyscus mice retained good sensitivity to sound across their lifespan. Middle-aged P. leucopus had comparable thresholds to young for frequencies below 24 kHz. P. leucopus also had notably large ABRs that were robust to age-related amplitude reductions, although response latencies increased with age. Old P. californicus were less sensitive to mid-range tones (8-16 kHz) than young individuals; however, there were no significant age-effects on ABR amplitudes or latencies in this species. These results indicate that longevity in Peromyscus mice may be correlated with delayed aging of the auditory system and highlight these species as promising candidates for longitudinal hearing research.

Corticofugal and Brainstem Functions Associated With Medial Olivocochlear Cholinergic Transmission.

Cholinergic transmission is essential for survival and reproduction, as it is involved in several physiological responses. In the auditory system, both ascending and descending auditory pathways are modulated by cholinergic transmission, affecting the perception of sounds. The auditory efferent system is a neuronal network comprised of several feedback loops, including corticofugal and brainstem pathways to the cochlear receptor. The auditory efferent system's -final and mandatory synapses that connect the brain with the cochlear receptor- involve medial olivocochlear neurons and outer hair cells. A unique cholinergic transmission mediates these synapses through α9/α10 nicotinic receptors. To study this receptor, it was generated a strain of mice carrying a null mutation of the Chrna9 gene (α9-KO mice), lacking cholinergic transmission between medial olivocochlear neurons and outer hair cells, providing a unique opportunity to study the role of medial olivocochlear cholinergic transmission in auditory and cognitive functions. In this article, we review behavioral and physiological studies carried out to research auditory efferent function in the context of audition, cognition, and hearing impairments. Auditory studies have shown that hearing thresholds in the α9-KO mice are normal, while more complex auditory functions, such as frequency selectivity and sound localization, are altered. The corticofugal pathways have been studied in α9-KO mice using behavioral tasks, evidencing a reduced capacity to suppress auditory distractors during visual selective attention. Finally, we discuss the evolutionary role of the auditory efferent system detecting vocalizations in noise and its role in auditory disorders, such as the prevention of age-related hearing loss.

Auditory Behavior in Adult-Blinded Mice.

Cross-modal plasticity occurs when the function of remaining senses is enhanced following deprivation or loss of a sensory modality. Auditory neural responses are enhanced in the auditory cortex, including increased sensitivity and frequency selectivity, following short-term visual deprivation in adult mice (Petrus et al. Neuron 81:664-673, 2014). Whether or not these visual deprivation-induced neural changes translate into improved auditory perception and performance remains unclear. As an initial investigation of the effects of adult visual deprivation on auditory behaviors, CBA/CaJ mice underwent binocular enucleation at 3-4 weeks old and were tested on a battery of learned behavioral tasks, acoustic startle response (ASR), and prepulse inhibition (PPI) tests beginning at least 2 weeks after the enucleation procedure. Auditory brain stem responses (ABRs) were also measured to screen for potential effects of visual deprivation on non-behavioral hearing function. Control and enucleated mice showed similar tone detection sensitivity and frequency discrimination in a conditioned lick suppression test. Both groups showed normal reactivity to sound as measured by ASR in a quiet background. However, when startle-eliciting stimuli were presented in noise, enucleated mice showed decreased ASR amplitude relative to controls. Control and enucleated mice displayed no significant differences in ASR habituation, PPI tests, or ABR thresholds, or wave morphology. Our findings suggest that while adult-onset visual deprivation induces cross-modal plasticity at the synaptic and circuit levels, it does not substantially influence simple auditory behavioral performance.

The Energy Homeostasis Principle: A Naturalistic Approach to Explain the Emergence of Behavior.

It is still elusive to explain the emergence of behavior and understanding based on its neural mechanisms. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding emerge. FEP starts from a whole-organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort but starts from single-neuron phenomena and builds up to whole-organism behavior and understanding. In this work, we further develop the EHP as a distinct but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of the function, purpose, and conception of goal-oriented behavior. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing by explaining basic learning scenarios up to simple anticipatory behavior. Finally, we end the article with an evolutionary perspective of how this non-goal-oriented behavior appeared. We acknowledge that our proposal, in its current form, is still far from explaining the emergence of understanding. Nonetheless, we set the ground for an alternative neuron-based framework to ultimately explain understanding.

Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System.

Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

The Strength of the Medial Olivocochlear Reflex in Chinchillas Is Associated With Delayed Response Performance in a Visual Discrimination Task With Vocalizations as Distractors.

The ability to perceive the world is not merely a passive process but depends on sensorimotor loops and interactions that guide and actively bias our sensory systems. Understanding which and how cognitive processes participate in this active sensing is still an open question. In this context, the auditory system presents itself as an attractive model for this purpose as it features an efferent control network that projects from the cortex to subcortical nuclei and even to the sensory epithelium itself. This efferent system can regulate the cochlear amplifier sensitivity through medial olivocochlear (MOC) neurons located in the brainstem. The ability to suppress irrelevant sounds during selective attention to visual stimuli is one of the functions that have been attributed to this system. MOC neurons are also directly activated by sounds through a brainstem reflex circuit, a response linked to the ability to suppress auditory stimuli during visual attention. Human studies have suggested that MOC neurons are also recruited by other cognitive functions, such as working memory and predictability. The aim of this research was to explore whether cognitive processes related to delayed responses in a visual discrimination task were associated with MOC function. In this behavioral condition, chinchillas held their responses for more than 2.5 s after visual stimulus offset, with and without auditory distractors, and the accuracy of these responses was correlated with the magnitude of the MOC reflex. We found that the animals' performance decreased in presence of auditory distractors and that the results observed in MOC reflex could predict this performance. The individual MOC strength correlated with behavioral performance during delayed responses with auditory distractors, but not without them. These results in chinchillas, suggest that MOC neurons are also recruited by other cognitive functions, such as working memory.