Biology subjects

Lujan, J. L.

Publications and source records attributed to Lujan, J. L..

3 recordsLinked to original sources

bioRxiv2021

An ultra-low frequency spike timing dependent plasticity-based approach for treating alcohol use disorder

Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol consumption despite adverse social, occupational, or health consequences. AUD affects nearly one-third of adults at some point during their lives, with an associated cost of approximately $249 billion annually in the U.S. alone. The effects of alcohol consumption are expected to increase significantly during the COVID-19 pandemic, with alcohol sales increased by approximately 54%, potentially exacerbating health concerns and risk-taking behaviors. Unfortunately, existing pharmacological and behavioral therapies for AUD have historically been associated with poor success rates, with approximately 40% of individuals relapsing within three years of treatment. Pre-clinical studies have shown that chronic alcohol consumption leads to significant changes in synaptic function within the dorsal medial striatum (DMS), one of the brain regions associated with AUD and responsible for mediating goal-directed behavior. Specifically, chronic alcohol consumption has been associated with hyperactivity of dopamine receptor 1 (D1) medium spiny neurons (MSN) and hypoactivity of dopamine receptor 2 (D1) MSNs within the DMS. Optogenetic, chemogenetic, and transgenic approaches have demonstrated that reducing the D1/D2 MSN signaling imbalance decreases alcohol self-administration in rodent models of AUD. However, these approaches cannot be studied clinically at this time. Here, we present an electrical stimulation alternative that uses ultra-low (<=1Hz) frequency (ULF) spike-timing dependent plasticity (STDP) to reduce DMS D1/D2 MSN signaling imbalances by stimulating D1-MSN afferents into the GPi and ACC glutamatergic projections to the DMS in a time-locked stimulation sequence. Our data suggest that GPi/ACC ULF-STDP selectively decreases DMS D1-MSN hyperactivity leading to reduced alcohol consumption without evoking undesired affective behaviors in a two-bottle choice mouse model of AUD.

neuroscience↗

bioRxiv2020

Integral methods for automatic quantification of fast-scan-cyclic-voltammetry detected neurotransmitters

Modern techniques for estimating basal levels of electroactive neurotransmitters rely on the measurement of oxidative charges. This requires time integration of oxidation currents at certain intervals. Unfortunately, the selection of integration intervals relies on ad-hoc visual identification of peaks on the oxidation currents, which introduces sources of error and precludes the development of automated procedures necessary for analysis and quantification of neurotransmitter levels in large data sets. In an effort to improve charge quantification techniques, here we present novel methods for automatic selection of integration boundaries. Our results show that these methods allow quantification of oxidation and reduction reactions, for multiple analytes, both in vitro and in vivo.

neuroscience↗

bioRxiv2019

A Truly Injectable Neural Stimulation Electrode Made From an In-Body Curing Polymer/Metal Composite

Implanted neural stimulation and recording devices hold vast potential to treat a variety of neurological conditions, but the invasiveness, complexity, and cost of the implantation procedure greatly reduce access to an otherwise promising therapeutic approach. To address this need, we have developed a novel electrode that begins as an uncured, flowable pre-polymer that can be injected around a neuroanatomical target to minimize surgical manipulation. Referred to as the Injectrode, the electrode conforms to target structures forming an electrically conductive interface which is orders of magnitude less stiff than conventional neuromodulation electrodes. To validate the Injectrode, we performed detailed electrochemical and microscopy characterization of its material properties and validated the feasibility of using it to electrically stimulate the nervous system in rats and swine. The silicone-metal-particle composite performed very similarly to pure wire of the same metal (silver) in all measures, including exhibiting a favorable cathodic charge storage capacity (CSCC) and charge injection limits compared to the clinical LivaNova stimulation electrode and silver wire electrodes. By virtue of being simpler than traditional electrode designs, less invasive, and more cost-effective, the Injectrode has the potential to increase the adoption of neuromodulation therapies for existing and new indications.

bioengineering↗