Biology subjects

Ward, A. L.

Publications and source records attributed to Ward, A. L..

3 recordsLinked to original sources

bioRxiv2024

Functional Electrical Stimulation and Brain-Machine Interfaces for Simultaneous Control of Wrist and Finger Flexion

Brain-machine interface (BMI) controlled functional electrical stimulation (FES) is a promising treatment to restore hand movements to people with cervical spinal cord injury. Recent intracortical BMIs have shown unprecedented successes in decoding user intentions, however the hand movements restored by FES have largely been limited to predetermined grasps. Restoring dexterous hand movements will require continuous control of many biomechanically linked degrees-of-freedom in the hand, such as wrist and finger flexion, that would form the basis of those movements. Here we investigate the ability to restore simultaneous wrist and finger flexion, which would enable grasping with a controlled hand posture and assist in manipulating objects once grasped. We demonstrate that intramuscular FES can enable monkeys with temporarily paralyzed hands to move their fingers and wrist across a functional range of motion, spanning an average 88.6 degrees at the metacarpophalangeal joint flexion and 71.3 degrees of wrist flexion, and intramuscular FES can control both joints simultaneously in a real-time task. Additionally, we demonstrate a monkey using an intracortical BMI to control the wrist and finger flexion in a virtual hand, both before and after the hand is temporarily paralyzed, even achieving success rates and acquisition times equivalent to able-bodied control with BMI control after temporary paralysis in two sessions. Together, this outlines a method using an artificial brain-to-body interface that could restore continuous wrist and finger movements after spinal cord injury. One Sentence SummaryWe show in non-human primates that intramuscular functional electrical stimulation can flex the wrist and fingers through a functional range of movement, can be controlled precisely, and that a brain-machine interface can determine command signals for intended finger and wrist flexion.

neuroscience↗

bioRxiv2024

Corticostriatal ensemble dynamics across heroin self-administration to reinstatement

Corticostriatal projection neurons from prelimbic medial prefrontal cortex to the nucleus accumbens core critically regulate drug-seeking behaviors, yet the underlying encoding dynamics whereby these neurons contribute to drug seeking remain elusive. Here we use two-photon calcium imaging to visualize the activity of corticostriatal neurons in mice from the onset of heroin use to relapse. We find that the activity of these neurons is highly heterogeneous during heroin self-administration and seeking, with at least 8 distinct neuronal ensembles that display both excitatory and inhibitory encoding dynamics. These neuronal ensembles are particularly apparent during relapse, where excitatory responses are amplified compared to heroin self-administration. Moreover, we find that optogenetic inhibition of corticostriatal projection neurons attenuates heroin seeking regardless of the relapse trigger. Our results reveal the precise corticostriatal activity dynamics underlying drug-seeking behaviors and support a key role for this circuit in mediating relapse to drug seeking.

neuroscience↗

bioRxiv2024

A Model of Ethanol Self-Administration in Head-Fixed Mice

BackgroundSignificant advances in neurotechnology, such as the application of two-photon (2P) imaging of biosensors in vivo, have enabled unparalleled longitudinal and high-resolution access to neural circuits that coordinate behavior in rodents. Integration of these techniques would be groundbreaking for the study of alcohol use disorder (AUD). AUD is rooted in significant neural adaptations that could be functionally monitored and manipulated at the single-cell level across development of dependence in rodents. However, 2P imaging and related methodologies often require or are facilitated by head-fixation, and a lack of head-fixed models have hindered their integration for the study of alcohol dependence. MethodsWe developed a head-fixed model in which animals learned to self-administer ethanol across [~]14 days. Active lever responding resulted in a tone cue and ethanol reward, whereas responding on the inactive lever resulted in neither cue nor ethanol reward. Following acquisition, animals extinguished lever pressing across a minimum of 10 days. And finally, animals were tested separately for both cue- and ethanol-induced reinstatement of lever pressing. ResultsHere we show, for the first time, that in our head-fixed ethanol self-administration model male and female mice reliably pressed an active, but not inactive, lever for an oral ethanol reward. Ethanol rewards positively correlated with blood ethanol concentrations, at pharmacologically relevant levels. Furthermore, mice extinguished ethanol self-administration when the ethanol reward and cue were omitted, suggesting active lever pressing was ethanol directed. Following extinction, presentation of the ethanol-associated cue or priming with ethanol itself invigorated reinstatement of ethanol seeking, modeling relapse in a manner that replicates decades of work in freely-moving rodent studies. ConclusionsOverall, our head-fixed ethanol self-administration model will allow for incorporation of novel technologies that require or are greatly facilitated by head-fixation, improving our ability to study and understand the neural adaptations and computations that underlie alcohol dependence.

animal behavior and cognition↗