bioRxiv Science⌕ Search

Biology subjects

Herron, J.

Publications and source records attributed to Herron, J..

4 recordsLinked to original sources

Cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain

The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.

developmental biology↗

DyNeuMo Mk-1: A Fully-Implantable, Motion-Adaptive Neurostimulator with Configurable Response Algorithms

There is growing interest in using adaptive neuro-modulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the Picostim DyNeuMo Mk-1 (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patients movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.

bioengineering↗

BioSkills Guide: Development and National Validation of a Tool for Interpreting the Vision and Change Core Competencies

To excel in modern STEM careers, biology majors need a range of transferrable skills, yet competency development is often a relatively underdeveloped facet of the undergraduate curriculum. Here, we have elaborated the Vision and Change core competency framework into a resource called the BioSkills Guide, a set of measurable learning outcomes that can be more readily interpreted and implemented by faculty. College biology educators representing over 250 institutions, including 73 community colleges, contributed to the development and validation of the guide. Our grassroots approach during the development phase engaged over 200 educators over the course of five iterative rounds of review and revision. We then gathered evidence of the BioSkills Guides content validity using a national survey of over 400 educators. Across the 77 outcomes in the final draft, rates of respondent support for outcomes were high (74.3% - 99.6%). Our national sample included college biology educators across a range of course levels, subdisciplines of biology, and institution types. We envision the BioSkills Guide supporting a variety of applications in undergraduate biology, including backward design of individual lessons and courses, competency assessment development, curriculum mapping and planning, and resource development for less well-defined competencies.

scientific communication and education↗

Global and local excitation and inhibition shape the dynamics of the cortico-striatal-thalamo-cortical pathway

The cortico-striatal-thalamo-cortical (CSTC) pathway is a brain circuit that controls movement execution, habit formation and reward. Hyperactivity in the CSTC pathway is involved in obsessive compulsive disorder, a neuropsychiatric disorder characterized by the execution of repetitive involuntary movements. The striatum shapes the activity of the CSTC pathway through the coordinated activation of two classes of medium spiny neurons (MSNs) expressing D1 or D2 dopamine receptors. The exact mechanisms by which balanced excitation/inhibition of these cells controls the network dynamics of the CSTC pathway remain unclear. Here we use non-linear modeling of neuronal activity and bifurcation theory to investigate how global and local changes in excitation/inhibition of MSNs regulate the activity of the CSTC pathway. Our findings indicate that a global and proportionate increase in excitation/inhibition pushes the system to states of generalized hyper-activity throughout the entire CSTC pathway. Certain disproportionate changes in global excitation/inhibition trigger network oscillations. Local changes in the excitation/inhibition of MSNs generate specific oscillatory behaviors in MSNs and in the CSTC pathway. These findings indicate that subtle changes in the relative strength of excitation/inhibition of MSNs can powerfully control the network dynamics of the CSTC pathway in ways that are not easily predicted by its synaptic connections.

neuroscience↗