A comparative perspective on three primate species’ responses to a pictorial emotional Stroop task

This study was also supported (in part) by a grant from The David Bohnett Foundation, the Leo S. Guthman Fund, the Chauncey and Marion Deering McCormick Foundation, and, at the time of writing, L.M.H. was supported by the Women’s Board of Lincoln Park Zoo.The Stroop effect describes interference in cognitive processing due to competing cognitive demands. Presenting emotionally laden stimuli creates similar Stroop-like effects that result from participants’ attention being drawn to distractor stimuli. Here, we adapted the methods of a pictorial Stroop study for use with chimpanzees (N = 6), gorillas (N = 7), and Japanese macaques (N = 6). We tested all subjects via touchscreens following the same protocol. Ten of the 19 subjects passed pre-test training. Subjects who reached criterion were then tested on a standard color-interference Stroop test, which revealed differential accuracy in the primates’ responses across conditions. Next, to test for an emotional Stroop effect, we presented subjects with photographs that were either positively valenced (a preferred food) or negatively valenced (snakes). In the emotional Stroop task, as predicted, the primates were less accurate in trials which presented emotionally laden stimuli as compared to control trials, but there were differences in the apes’ and monkeys’ response patterns. Furthermore, for both Stroop tests, while we found that subjects’ accuracy rates were reduced by test stimuli, in contrast to previous research, we found no difference across trial types in the subjects’ response latencies across conditions.Publisher PDFPeer reviewe

Identification of sequence changes in myosin II that adjust muscle contraction velocity.

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (β/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of β-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human β-myosin to match the rat sequence. Biochemical analysis revealed that the rat-human β-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin-myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of β-myosin as species mass increased to enable a reduced contraction velocity and heart rate

Neurotransmission defines functional chemosensory neural circuits to regulate behavior

Neural circuits detect and process environmental changes to drive appropriate food-seeking or toxin-avoiding behaviors. However, we lack a complete understanding of the cellular and molecular mechanisms that represent chemosensory cues and generate appropriate behaviors. Furthermore, these vital sensory abilities deteriorate with age in humans and most animals, but it is unknown how aging impairs the underlying neural circuits to cause sensory behavioral declines. With powerful genetic tools, a complete connectome and robust chemosensory behaviors, the nematode Caenorhabditis elegans is ideally suited for a circuit-level analysis of these behaviors in young and aged animals. The aim of this dissertation is to identify neural signaling and circuit principles for flexibly encoding chemosensory stimuli and generating behavioral plasticity in C. elegans, which may be broadly conserved. In Chapters 2 and 3, I define a novel, sensory context- dependent and neuropeptide-regulated switch in the composition of a C. elegans salt sensory circuit. The ASE primary salt sensory neurons cleave and release insulin- like peptides in response to large but not small changes in external salt stimuli. Insulin signaling functionally switches the AWC olfactory sensory neuron into an interneuron in the high salt circuit, potentiating behavioral responses. Thus, sensory context and neuropeptide signaling act together to shape the flow of information in active neural circuits, suggesting a general mechanism for generating dynamic behavioral outputs. In Chapter 4, I identify an aging-associated decline in C. elegans olfactory behavior and map a novel underlying circuit motif. Two primary olfactory sensory neuron pairs, AWC and AWA, directly detect benzaldehyde and release insulin peptides and acetylcholine to activate two secondary neuron pairs, ASE and AWB, and drive behavioral plasticity. Interestingly, odor-evoked activity in the secondary, but not primary, neurons degrades with age. Experimental manipulations to increase primary neuron transmitter release rescue these aging-associated neuronal deficits. Furthermore, aged animals' olfactory abilities are correlated with lifespan, suggesting that olfaction may be indicative of overall health and physiology. These results show how chemosensory stimuli are encoded by a population code composed of primary and secondary neurons and suggest reduced neurotransmission as a novel mechanism driving aging-associated sensory neural activity and behavioral declines. In sum, this dissertation establishes the crucial role of peptidergic and classical neurotransmission in defining the active neural circuit configurations that regulate chemosensory behavior

Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior

Mature behaviors emerge from neural circuits sculpted by genetic programs and spontaneous and evoked neural activity. However, how neural activity is refined to drive maturation of learned behavior remains poorly understood. Here, we explore how transient hormonal signaling coordinates a neural activity state transition and maturation of associative learning. We identify spontaneous, asynchronous activity in a Drosophila learning and memory brain region, the mushroom body. This activity declines significantly over the first week of adulthood. Moreover, this activity is generated cell-autonomously via Cacophony voltage-gated calcium channels in a single cell type, α'/β' Kenyon cells. Juvenile hormone, a crucial developmental regulator, acts transiently in α'/β' Kenyon cells during a young adult sensitive period to downregulate spontaneous activity and enable subsequent enhanced learning. Hormone signaling in young animals therefore controls a neural activity state transition and is required for improved associative learning, providing insight into the maturation of circuits and behavior

Capuchin (Sapajus [Cebus] apella) Change Detection

Change blindness is a phenomenon in which individuals fail to detect seemingly obvious changes in their visual fields.  Like humans, several animal species have also been shown to exhibit change blindness; however, no species of New World monkey has been tested to date.  Nine capuchins ( Sapajus [Cebus] apella ) were trained to select whether or not a stimulus changed on a computerized task.  In four phases of testing, consisting of full image changes, subtle occlusion changes, and two levels of feature location changes, the search display and mask durations were systematically varied to determine whether capuchins experienced change blindness and in what contexts.  Only the full image change test yielded significant results, with subjects detecting changes most accurately with longer search displays and, perplexingly, least accurately when there was no mask.  No interactions between search display and mask durations were found in any test phase, suggesting that the relationship between the two parameters may not be important to how capuchins perceive changes.  While it is possible that capuchins do not experience change blindness, we suspect that a mix of experimental design, the difficulty of the task, and the inability to verify how closely the subjects attended to each trial contributed to the lack of significant results

A comparative perspective on three primate species’ responses to a pictorial emotional Stroop task

The Stroop effect describes interference in cognitive processing due to competing cognitive demands. Presenting emotionally laden stimuli creates similar Stroop-like effects that result from participants’ attention being drawn to distractor stimuli. Here, we adapted the methods of a pictorial Stroop study for use with chimpanzees (N = 6), gorillas (N = 7), and Japanese macaques (N = 6). We tested all subjects via touchscreens following the same protocol. Ten of the 19 subjects passed pre-test training. Subjects who reached criterion were then tested on a standard color-interference Stroop test, which revealed differential accuracy in the primates’ responses across conditions. Next, to test for an emotional Stroop effect, we presented subjects with photographs that were either positively valenced (a preferred food) or negatively valenced (snakes). In the emotional Stroop task, as predicted, the primates were less accurate in trials which presented emotionally laden stimuli as compared to control trials, but there were differences in the apes’ and monkeys’ response patterns. Furthermore, for both Stroop tests, while we found that subjects’ accuracy rates were reduced by test stimuli, in contrast to previous research, we found no difference across trial types in the subjects’ response latencies across conditions

Redirecting Valvular Myofibroblasts into Dormant Fibroblasts through Light-mediated Reduction in Substrate Modulus

<div><p>Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young’s modulus of the substrate was reduced from ∼32 kPa, mimicking pre-calcified diseased tissue, to ∼7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of <em>in situ</em> substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing hydrogel substrates with physiologically relevant stiffness to dynamically redirect cell fate <em>in vitro.</em></p> </div

Deactivated VICs on stiff-to-soft gels enter the cell cycle with proliferative stimulus and activate myofibroblast the gene program in response to TGF-β1.

<p>VICs cultured on stiff-to-soft gels were treated with either proliferative media with 15% FBS and fibroblast growth factor 2 (FGF-2) or fibrogenic chemokine (TGF-β1) on day 4 for 24 hours. (A) Proliferation was measured by EdU chase for 1 hour on day 5. VICs treated with growth stimulus had ∼4 fold more proliferating cells than those in control medium. (B) Myofibroblast gene markers, including CTGF, collagen 1a1 (Col1a1) and fibronectin 1 (FN1), were significantly up-regulated in deactivated VICs treated with TGF-β1. The mRNA level of α-SMA was not changed significantly by TGF-β1 treatment. (C) Immunocytochemistry of α-SMA showed similar levels of myofibroblasts on stiff-to-soft gels treated with or without TGF-β1. Green: α-SMA. Blue: nuclei. These results show that the de-activated fibroblasts have the potential to proliferate and to activate fibrogenic associated genes in response to chemical cues, but a stiffer substratum is likely required for α-SMA stress fiber formation. Scale bar: 100 µm. * indicates p<0.05.</p