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Bartholomew, R.

Publications and source records attributed to Bartholomew, R..

2 recordsLinked to original sources

Interaction of micropatterned topographical and biochemical cues to direct neurite growth from spiral ganglion neurons

Functional outcomes with neural prosthetic devices, such as cochlear implants, are limited in part due to physical separation between the stimulating elements and the neurons they stimulate. One strategy to close this gap aims to precisely guide neurite regeneration to position the neurites in closer proximity to electrode arrays. Here, we explore the ability of micropatterned biochemical and topographic guidance cues, singly and in combination, to direct the growth of spiral ganglion neuron (SGN) neurites, the neurons targeted by cochlear implants. Photopolymerization of methacrylate monomers was used to form unidirectional topographical features of ridges and grooves in addition to multidirectional patterns with 90{degrees} angle turns. Microcontact printing was also used to create similar uni- and multi-directional patterns of peptides on polymer surfaces. Biochemical cues included peptides that facilitate (laminin, LN) or repel (EphA4-Fc) neurite growth. On flat surfaces, SGN neurites preferentially grew on LN-coated stripes and avoided EphA4-Fc-coated stripes. LN or EphA4-Fc was selectively adsorbed onto the ridges or grooves to test the neurite response to a combination of topographical and biochemical cues. Coating the ridges with EphA4-Fc and grooves with LN lead to enhanced SGN alignment to topographical patterns. Conversely, EphA4-Fc coating on the grooves or LN coating on the ridges tended to disrupt alignment to topographical patterns. SGN neurites respond to combinations of topographical and biochemical cues and surface patterning that leverages both cues enhance guided neurite growth.

bioengineering↗

Hypothalamic-extended amygdala circuit regulates temporal discounting

Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards over delayed rewards. Temporal discounting is often dysfunctional in psychiatric disorders, addiction, and eating disorders. However, the underlying neural mechanisms governing temporal discounting are still poorly understood. We found that food deprivation resulted in steep temporal discounting of food rewards, whereas satiation abolished discounting. In addition, optogenetic activation of AgRP-expressing neurons in the arcuate nucleus or their axon terminals in the posterior bed nucleus of stria terminalis (BNST) restored temporal discounting in sated mice. Activation of postsynaptic neuropeptide Y receptors (Y1Rs) within the BNST, which is influenced by neuropeptide released by AgRP neurons, was sufficient to restore temporal discounting. These results demonstrate for the first time a profound effect of motivational signals from hypothalamic feeding circuits on temporal discounting and reveal a novel neural circuit that regulates choice behavior.

neuroscience↗