Characterizing the genetic basis of trait evolution in the Mexican cavefish

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabits the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism and enhanced mechanosensory function. The infertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of behavioral and morphological traits. Taken together, this approach provides a novel system to identify genes that underlie naturally occurring genetic variation in morphological and behavioral traits.

Response triggering by an acoustic stimulus increases with stimulus intensity and is best predicted by startle reflex activation

In a simple reaction time task, the presentation of a startling acoustic stimulus has been shown to trigger the prepared response at short latency, known as the StartReact effect. However, it is unclear under what conditions it can be assumed that the loud stimulus results in response triggering. The purpose of the present study was to examine how auditory stimulus intensity and preparation level affect the probability of involuntary response triggering and the incidence of activation in the startle reflex indicator of sternocleidomastoid (SCM). In two reaction time experiments, participants were presented with an irrelevant auditory stimulus of varying intensities at various time points prior to the visual go-signal. Responses were independently categorized as responding to either the auditory or visual stimulus and those with or without SCM activation (i.e., SCM+/−). Both the incidence of response triggering and proportion of SCM+ trials increased with stimulus intensity and presentation closer to the go-signal. Data also showed that participants reacted to the auditory stimulus at a much higher rate on trials where the auditory stimulus elicited SCM activity versus those that did not, and a logistic regression analysis confirmed that SCM activation is a reliable predictor of response triggering for all conditions.

Light-stimulus intensity modulates startle reflex habituation in larval zebrafish

The startle reflex in larval zebrafish describes a C-bend of the body occurring in response to sudden, unexpected, stimuli of different sensory modalities. Alterations in the startle reflex habituation (SRH) have been reported in various human and animal models of neurological and psychiatric conditions and are hence considered an important behavioural marker of neurophysiological function. The amplitude, offset and decay constant of the auditory SRH in larval zebrafish have recently been characterised, revealing that the measures are affected by variation in vibratory frequency, intensity, and interstimulus-interval. Currently, no study provides a model-based analysis of the effect of physical properties of light stimuli on the visual SRH. This study assessed the effect of incremental light-stimulus intensity on the SRH of larval zebrafish through a repeated-measures design. Their total locomotor responses were normalised for the time factor, based on the behaviour of a (non-stimulated) control group. A linear regression indicated that light intensity positively predicts locomotor responses due to larger SRH decay constants and offsets. The conclusions of this study provide important insights as to the effect of light properties on the SRH in larval zebrafish. Our methodology and findings constitute a relevant reference framework for further investigation in translational neurophysiological research.

Emotional reactivity to binge food and erotic cues in women with bulimia nervosa symptoms

Background Studies on food cue reactivity have documented that altered responses to high-calorie food are associated with bulimic symptomatology, however, alterations in sexual motivations and behaviors are also associated clinical features in this population, which justify their inclusion as a research target. Here, we study responses to erotic cues—alongside food, neutral and aversive cues—to gain an understanding of specificity to food versus a generalized sensitivity to primary reinforcers. Methods We recorded peripheral psychophysiological indices –the startle reflex, zygomaticus, and corrugator responses—and self-reported emotional responses (valence, arousal, and dominance) in 75 women completing the Bulimia Test-Revised (BULIT-R). Multiple regression analysis tested whether BULIT-R symptoms were predicted by self-reported and psychophysiological responses to food versus neutral and erotic versus neutral images. Results The results showed that individuals with higher bulimic symptoms were characterized by potentiated eye blink startle response during binge food (vs. neutral images) and more positive valence ratings during erotic (vs. neutral) cues. Conclusions The results highlight the negative emotional reactivity of individuals with elevated bulimic symptoms toward food cues, which could be related to the risk of progression to full bulimia nervosa and thereby addressed in prevention efforts. Results also point to the potential role of reactivity to erotic content, at least on a subjective level. Theoretical models of eating disorders should widen their conceptual scope to consider reactivity to a broader spectrum of primary reinforcers, which would have implications for cue exposure-based treatments. Plain English summary We examined appetitive and aversive cue responses in college women to investigate how bulimic symptoms relate to primary reinforcers such as food and erotic images. We recorded peripheral psychophysiological indices (the startle reflex, zygomaticus, and corrugator responses) and self-reported emotional responses (valence, arousal, and dominance) in 75 college women that were presented with the Spanish version of the Bulimia Test-Revised. The results showed that bulimic symptoms increase both psychophysiological defensiveness toward food cues and subjective pleasure toward erotic cues. The findings suggest a generalized sensitivity to primary reinforcers in the presence of bulimic symptoms, and emphasize the relevance of adopting a wider framework in research and treatment on bulimia nervosa.

EFFECTS OF AGMATINE ON ACOUSTIC STARTLE REFLEX AND AUDITORY SYSTEM IN RATS

Background: A polyamine, agmatine, has been proposed as a new neurotransmitter in the brain. Objective: The aim of this study was to evaluate the effects of acute and chronic agmatine treatment on the rat auditory system. Methods: Male Wistar albino rats weighing between 280-330 grams were used. Animals were divided into four groups (n= 8 for each group). Acute and chronic agmatine (160 mg/kg) was administered to rats. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR), distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABR) were evaluated in all groups. Results: Both acute and chronic agmatine treatments also significantly disrupted PPI. Chronic but not acute treatment with agmatine produced some DPOAE and ABR changes in rats. Conclusion: Our results suggested that chronic agmatine treatment for seven days resulted in some significant negative changes in cochlear function. Because the PPI of the ASR is also used as an indicator for psychoses, such as schizophrenia, in human and experimental animal studies, our findings also imply that the DPOAE and ABR tests may also be considered in the diagnosis and follow-up of patients with psychoses.

Immediate Effect of Primal Reflex Release Technique on Heart Rate Variability in Chronic Neck Pain: A Case Report

Primal reflex release technique (PRRT) is a paradigm shift in the treatment of pain which follows the principle of rebooting the autonomous nervous system (ANS), by down regulating the upgraded sympathetic component of ANS in a variety of pain syndromes. To check the effect of PRRT on chronic neck pain, a case study was done using Heart Rate Variability (HRV) and Visual Analogue Scale (VAS) as outcome measures. After conducting the one minute nociceptive exam for startle reflex, indication of the upgraded Sympathetic Nervous System (SNS), a single session of PRRT was carried out on a 24 year old female patient with chronic neck pain having a VAS score of 7 on activity and that of 5 on rest. Pre and post treatment HRV analysis was done using frequency domain and time domain parameters. Post PRRT treatment, an improvement in VAS scale with a score of 4 on activity and that of 3 on rest was seen. HRV showed a decrease in HFnu (26.7 vs 24.5), RMSSD (63.553 vs 59.216), SDNN (28.58 vs 34.82) and PNN50 (48.3 vs 42.5) which refers to decreased parasympathetic activity, and increased LFnu (73.3 vs 75.5) which indicates increased sympathetic activity. This was the first study evaluating the effect of PRRT with HRV. Further research needs to be conducted to validate HRV findings in chronic pain patients undergoing PRRT using a large sample size and interval based assessment of HRV. Key words: Neck Pain, Primal reflex release technique, Startle Reflex, Heart Rate Variability.

The amygdala modulates prepulse inhibition of the auditory startle reflex through excitatory inputs to the caudal pontine reticular nucleus

Background Sensorimotor gating is a fundamental pre-attentive process that is defined as the inhibition of a motor response by a sensory event. Sensorimotor gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders. PPI deficits are a hallmark of schizophrenia, and they are often associated with attention and other cognitive impairments. Although the reversal of PPI deficits in animal models is widely used in pre-clinical research for antipsychotic drug screening, the neurotransmitter systems and synaptic mechanisms underlying PPI are still not resolved, even under physiological conditions. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic, and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since amygdalar dysfunctions alter PPI and are common to pathologies displaying sensorimotor gating deficits, the present study was designed to test that direct projections to the PnC originating from the amygdala contribute to PPI. Results Using wild type and transgenic mice expressing eGFP under the control of the glycine transporter type 2 promoter (GlyT2-eGFP mice), we first employed tract-tracing, morphological reconstructions, and immunohistochemical analyses to demonstrate that the central nucleus of the amygdala (CeA) sends glutamatergic inputs lateroventrally to PnC neurons, including GlyT2+ cells. Then, we showed the contribution of the CeA-PnC excitatory synapses to PPI in vivo by demonstrating that optogenetic inhibition of this connection decreases PPI, and optogenetic activation induces partial PPI. Finally, in GlyT2-Cre mice, whole-cell recordings of GlyT2+ PnC neurons in vitro paired with optogenetic stimulation of CeA fibers, as well as photo-inhibition of GlyT2+ PnC neurons in vivo, allowed us to implicate GlyT2+ neurons in the PPI pathway. Conclusions Our results uncover a feedforward inhibitory mechanism within the brainstem startle circuit by which amygdalar glutamatergic inputs and GlyT2+ PnC neurons contribute to PPI. We are providing new insights to the clinically relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurological diseases.