open-source-real-time-closed-loop-electrical-threshold-tracking-for

Open-Source Real-Time Closed-Loop Electrical Threshold Tracking for Translational Pain Research

Nociceptors are a class of primary afferent neurons that signal potentially harmful noxious stimuli. An increase in nociceptor excitability occurs in ...

University of Bristol

Microneurography is the only method for recording from single neurons in intact human nerves. It is challenging - requiring technical expertise, investment in specialised equipment and has sparse data yields.

Ultrasound-guided, open-source microneurography: Approaches to improve recordings from peripheral nerves in man.

The locus coeruleus (LC) in the pons is the major source of noradrenaline (NA) in the brain. Two modes of LC firing have been associated with distinct cognitive states: changes in tonic rates of firing are correlated with global levels of arousal and behavioural flexibility, whilst phasic LC responses are evoked by salient stimuli. Here, we unify these two modes of firing by modelling the response of the LC as a correlate of a prediction error when inferring states for action planning under Active Inference (AI). We simulate a classic Go/No-go reward learning task and a three-arm 'explore/exploit' task and show that, if LC activity is considered to reflect the magnitude of high level 'state-action' prediction errors, then both tonic and phasic modes of firing are emergent features of belief updating. We also demonstrate that when contingencies change, AI agents can update their internal models more quickly by feeding back this state-action prediction error-reflected in LC firing and noradrenaline release-to optimise learning rate, enabling large adjustments over short timescales. We propose that such prediction errors are mediated by cortico-LC connections, whilst ascending input from LC to cortex modulates belief updating in anterior cingulate cortex (ACC). In short, we characterise the LC/ NA system within a general theory of brain function. In doing so, we show that contrasting, behaviour-dependent firing patterns are an emergent property of the LC that translates state-action prediction errors into an optimal balance between plasticity and stability.

Locus Coeruleus tracking of prediction errors optimises cognitive flexibility: An Active Inference model.

Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating Barrington's nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. Barr neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRH mice show that Barr neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.

Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons.

Recordings of electrical activity in nerves have provided valuable insights into normal function and pathological behaviours of the nervous system. Current high-resolution techniques (e.g. teased fibre recordings) typically utilise electrodes with a single recording site, capturing the activity of a single isolated neuron per recording.

Article	Year
Ultrasound-guided, open-source microneurography: Approaches to improve recordings from peripheral nerves in man. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 30107982	2018
Locus Coeruleus tracking of prediction errors optimises cognitive flexibility: An Active Inference model. PLoS computational biology\| PubMed ID: 30608922	2019
Probabilistic, spinally-gated control of bladder pressure and autonomous micturition by Barrington's nucleus CRH neurons. eLife\| PubMed ID: 32347794	2020
Multisite silicon probes enable simultaneous recording of spontaneous and evoked activity in multiple isolated C-fibres in rat saphenous nerve. Journal of neuroscience methods\| PubMed ID: 34800543	2022

Anna C. Sales

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