Biology subjects

Stebbins, K.

Publications and source records attributed to Stebbins, K..

6 recordsLinked to original sources

bioRxiv2025

Novel major loci shape habitat-associated flowering time variation in Yellowstone monkeyflowers

O_LIPlants harbor remarkable genetic diversity in flowering phenology, particularly in their responses to environmental cues such as photoperiod. Understanding the genetic basis of repeated evolution in flowering cues, which are key to reproduction, illuminates adaptation with gene flow and parallel evolution. C_LIO_LIWe characterized variation in minimum critical daylength for flowering (MCD) in yellow monkeyflower (Mimulus guttatus) accessions from a geothermal soil mosaic in Yellowstone National Park, mapped loci underlying the most extreme MCD in focal thermal annuals, and investigated environmental variables shaping phenology in the field. C_LIO_LIYellowstone monkeyflowers range in MCD from 12-15 hours, paralleling range-wide variation in M. guttatus; plants from thermal habitats flower under significantly shorter daylengths. Two QTLs govern the most extreme 12-hour MCD. Both contain candidates from gene families previously implicated in phenological evolution in monkeyflowers and other angiosperms, but the major loci appear novel. The frequency of 12-hour flowering across a microgeographic gradient is predicted by variation in soil temperature and the timing of dry-down. C_LIO_LIAdaptation to Yellowstones geothermal soil mosaic has generated dramatic evolution of flowering cues over short spatial scales. The genetic basis of 12-hour flowering does not indicate re-use of known M. guttatus alleles, but strong candidate genes nonetheless suggest molecular parallelism. C_LI

evolutionary biology↗

bioRxiv2024

Retinal input is required for the maintenance of neuronal laminae in the ventral lateral geniculate nucleus

Retinal ganglion cell (RGC) axons provide direct input into several nuclei of the mouse visual thalamus, including the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and the ventral lateral geniculate nucleus (vLGN), which is associated with non-image-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), the timing of corticogeniculate innervation, and the recruitment of inhibitory interneurons from progenitor zones. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and the non-retinorecipient internal vLGN (vLGNi). We previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes that are distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for the formation and maintenance of these laminae in the mouse vLGNe and results indicate that these laminae are specified at or before birth, well before eye-opening and the emergence of experience-dependent visual activity. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell type-specific layers in vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.

neuroscience↗

bioRxiv2023

Non-invasive modulation of the human dorsal anterior cingulate attenuates acute pain perception and homeostatic cardiovascular responses

Homeostasis is the process of maintaining physiologic balance in the body that is critical for maintaining health and is dysfunctional in several disorders like chronic pain. The dorsal anterior cingulate cortex (dACC) is a critical brain area for homeostatic cardiovascular responses and pain processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for an effect on behavioral and cardiac autonomic responses using a transient heat pain stimulus. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included perceived pain ratings, homeostatic measures including heart-rate variability, blood pressure, EDR response as well as the amplitude of the contact heat-evoked potential (CHEP). LIFU reduced pain ratings by 1.08 {+/-} 0.21 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 25.1% reduction in the N1-P1 CHEP amplitude driven primarily by effects on the P1 amplitude. Our results demonstrate LIFU to the dACC reduces perceived pain and alters homeostatic cardiovascular responses to a transient heat pain stimulus. These results have implications for the causal understanding of human pain and autonomic processing in the dACC and the potential for future therapeutics for pain relief and homeostatic modulation. SIGNIFICANCE STATEMENTNew lines of inquiry now demonstrate cardiac homeostatic signals like heart rate variability (HRV) are aberrant in mental health disorders, addiction, and chronic pain and may contribute to their underlying etiology. The dorsal anterior cingulate cortex (dACC) is a key homeostatic center with direct influences on cardiovascular autonomic function, but its depth precludes direct access without invasive surgery. For the first time in humans, we demonstrate low-intensity focused ultrasound (LIFU) can non-invasively and selectively modulate the dACC to reduce acute pain perception and homeostatic cardiovascular responses as well as pain processing signals. This work helps establish a causal role of the dACC in pain perception and homeostatic signaling with potential future clinical applications in chronic pain and neuropsychological populations.

neuroscience↗

bioRxiv2023

Non-invasive neuromodulation of sub-regions of the human insula differentially affect pain processing and heart-rate variability

The insula is a portion of the cerebral cortex folded deep within the lateral sulcus covered by the overlying opercula of the inferior frontal lobe and superior portion of the temporal lobe. The insula has been parsed into sub-regions based upon cytoarchitectonics and structural and functional connectivity with multiple lines of evidence supporting specific roles for each of these sub-regions in pain processing and interoception. In the past, causal interrogation of the insula was only possible in patients with surgically implanted electrodes. Here, we leverage the high spatial resolution combined with the deep penetration depth of low-intensity focused ultrasound (LIFU) to non-surgically modulate either the anterior insula (AI) or posterior insula (PI) in humans for effect on subjective pain ratings, electroencephalographic (EEG) contact head evoked potentials (CHEPs) and time-frequency power as well as autonomic measures including heart-rate variability (HRV) and electrodermal response (EDR). N = 23 healthy volunteers received brief noxious heat pain stimuli to the dorsum of their right hand during continuous heart-rate, EDR and EEG recording. LIFU was delivered to either the AI (anterior short gyrus), PI (posterior longus gyrus) or under an inert sham condition time-locked to the heat stimulus. Results demonstrate that single-element 500 kHz LIFU is capable of individually targeting specific gyri of the insula. LIFU to both AI and PI similarly reduced perceived pain ratings but had differential effects on EEG activity. LIFU to PI affected earlier EEG amplitudes around 300 milliseconds whereas LIFU to AI affected EEG amplitudes around 500 milliseconds. In addition, only LIFU to the AI affected HRV as indexed by an increase in standard deviation of N-N intervals (SDNN) and mean HRV low frequency power. There was no effect of LIFU to either AI or PI on EDR or blood pressure. Taken together, LIFU looks to be an effective method to individually target sub-regions of the insula in humans for site-specific effects on brain biomarkers of pain processing and autonomic reactivity that translates to reduced perceived pain to a transient heat stimulus. These data have implications for the treatment of chronic pain and several neuropsychological diseases like anxiety, depression and addiction that all demonstrate abnormal activity in the insula concomitant with dysregulated autonomic function.

neuroscience↗

bioRxiv2022

Deficiency in the cell-adhesion molecule dscaml1 impairs hypothalamic CRH neuron development and neuroendocrine stress axis function

The corticotropin-releasing hormone (CRH)-expressing neurons in the hypothalamus are critical regulators of the neuroendocrine stress response pathway, known as the hypothalamic-pituitary-adrenal (HPA) axis. As developmental vulnerabilities of CRH neurons contribute to stress-associated neurological and behavioral dysfunctions, it is critical to identify the mechanisms underlying normal and abnormal CRH neuron development. Using zebrafish, we identified Down syndrome cell adhesion molecule like-1 (dscaml1) as an integral mediator of CRH neuron development and necessary for establishing normal stress axis function. In dscaml1 mutant animals, hypothalamic CRH neurons had higher crhb (the CRH homolog in fish) expression, increased cell number, and reduced cell death compared to wild-type controls. Physiologically, dscaml1 mutant animals had higher baseline stress hormone (cortisol) levels and attenuated responses to acute stressors. Together, these findings identify dscaml1 as an essential factor for stress axis development and suggest that HPA axis dysregulation may contribute to the etiology of human DSCAML1 -linked neuropsychiatric disorders.

developmental biology↗

bioRxiv2022

Sonic hedgehog-dependent recruitment of GABAergic interneurons into the developing visual thalamus

Axons of retinal ganglion cells (RGCs) play critical roles in the development of inhibitory circuits in visual thalamus. We previously reported that RGC axons signal astrocytes to induce the expression of fibroblast growth factor 15 (FGF15), a motogen required for GABAergic interneuron migration into visual thalamus. However, how retinal axons induce thalamic astrocytes to generate Fgf15 and influence interneuron migration remains unknown. Here, we demonstrate that impairing RGC activity had little impact on interneuron recruitment into mouse visual thalamus. Instead, our data show that retinal-derived sonic hedgehog (SHH) is essential for interneuron recruitment. Specifically, we show that thalamus-projecting RGCs express SHH and thalamic astrocytes generate downstream components of SHH signaling. Deletion of RGC-derived SHH leads to a significant decrease in Fgf15 expression, as well as in the percentage of interneurons recruited into visual thalamus. Thus, our findings identify a morphogen-dependent neuron-astrocyte signaling mechanism essential for the migration of thalamic interneurons.

neuroscience↗