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The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. ...

Radboud University

3D Neuro B.V.

Ernst-Strüngmann Institute for Neuroscience

Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group "PRISM", tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer's disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues.

Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection.

Controlling aggression is a crucial skill in social species like rodents and humans and has been associated with anterior cingulate cortex (ACC). Here, we directly link the failed regulation of aggression in BALB/cJ mice to ACC hypofunction. We first show that ACC in BALB/cJ mice is structurally degraded: neuron density is decreased, with pervasive neuron death and reactive astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then triggers toxic astrogliosis. cFos expression across ACC indicated functional consequences: during aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed pathological aggression but left species-typical aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioral rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the central role of ACC in curbing pathological aggression.

A central role for anterior cingulate cortex in the control of pathological aggression.

Trial-averaged metrics, e.g. tuning curves or population response vectors, are a ubiquitous way of characterizing neuronal activity. But how relevant are such trial-averaged responses to neuronal computation itself? Here we present a simple test to estimate whether average responses reflect aspects of neuronal activity that contribute to neuronal processing. The test probes two assumptions implicitly made whenever average metrics are treated as meaningful representations of neuronal activity: Reliability: Neuronal responses repeat consistently enough across trials that they convey a recognizable reflection of the average response to downstream regions.Behavioural relevance: If a single-trial response is more similar to the average template, it is more likely to evoke correct behavioural responses. We apply this test to two data sets: (1) Two-photon recordings in primary somatosensory cortices (S1 and S2) of mice trained to detect optogenetic stimulation in S1; and (2) Electrophysiological recordings from 71 brain areas in mice performing a contrast discrimination task. Under the highly controlled settings of Data set 1, both assumptions were largely fulfilled. In contrast, the less restrictive paradigm of Data set 2 met neither assumption. Simulations predict that the larger diversity of neuronal response preferences, rather than higher cross-trial reliability, drives the better performance of Data set 1. We conclude that when behaviour is less tightly restricted, average responses do not seem particularly relevant to neuronal computation, potentially because information is encoded more dynamically. Most importantly, we encourage researchers to apply this simple test of computational relevance whenever using trial-averaged neuronal metrics, in order to gauge how representative cross-trial averages are in a given context.

Martha N. Havenith

Donders Institute for Brain,
Cognition and Behaviour,
Donders Institute for Brain, Cognition and Behaviour

Radboud University

The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Martha N. Havenith

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Radboud University

The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Donders Institute for Brain,
Cognition and Behaviour,
Donders Institute for Brain, Cognition and Behaviour