Biology subjects

Kaetzel, D.

Publications and source records attributed to Kaetzel, D..

3 recordsLinked to original sources

bioRxiv2024

Excitatory neurons of the anterior cingulate cortex encode chosen actions and their outcomes rather than cognitive state

The anterior cingulate cortex (ACC) causally influences cognitive control of goal-directed behaviour. However, it is unclear whether ACC directly encodes cognitive variables like attention or impulsivity, or implements goal-directed action selection mechanisms that are modulated by them. We recorded ACC activity with miniature endoscopic microscopes in mice performing the 5-choice-serial-reaction time task, and applied decoding and encoding analyses. ACC pyramidal cells represented specific actions before and during the behavioural response, whereas the response type (e.g. correct/incorrect/premature) - indicating the state of attentional and impulse control - could only be decoded during and after the response with high reliability. Devaluation and extinction experiments further revealed that action encoding depended on reward expectation. Our findings support a role for ACC in goal-directed action selection and monitoring, that is modulated by cognitive state, rather than in tracking levels of attention or impulsivity directly in individual trials.

neuroscience↗

bioRxiv2020

Lack of redundancy between electrophysiological measures of long-range neuronal communication

Communication between brain areas has been implicated in a wide range of cognitive and emotive functions and is impaired in numerous mental disorders. In rodent models, various functional connectivity metrics have been used to quantify inter-regional neuronal communication. However, in individual studies, typically only very few measures of coupling are reported and, hence, redundancy across such indicators is implicitly assumed. In order to test this assumption, we here comparatively assessed a broad range of directional and non-directional metrics like coherence, weighted Phase-Lag-Index (wPLI), Granger causality (GC), spike-phase coupling (SPC), cross-regional phase-amplitude coupling, amplitude cross-correlations, and others. We applied these analyses to simultaneous field recordings from the prefrontal cortex and the ventral and dorsal hippocampus in the schizophrenia-related Gria1-knockout mouse model which displays a robust novelty-induced hyperconnectivity phenotype. We find that across such measures there is a considerable lack of functional redundancy. While coherence and GC yielded similar results, other measures, especially wPLI and SPC, often produced deviating conclusions. Bivariate correlations within animals revealed that virtually none of the metrics consistently co-varied with any of the other measures across the three connections and two genotypes analysed. Parametric GC showed the qualitatively highest degree of redundancy with other metrics and would be most suitable for connectivity analysis. We conclude that analysis of multiple metrics is necessary to characterise functional connectivity.

neuroscience↗

bioRxiv2018

Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model of ventral hippocampal hyperactivity

Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from its prodromal to its psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal Parvalbumin-interneuron dysfunction and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients. In a comprehensive phenotyping of CD2-KO mice, we found that they displayed novelty-induced hyperlocomotion (a correlate in the positive symptom domain), that was largely resistant against D1- and D2-dopamine receptor antagonism, but responsive to the mGluR2/3-agonist LY379268. In the negative symptom domain, CD2-KO mice showed transiently reduced sucrose-preference (anhedonia), but enhanced interaction with novel mice and objects, as well as normal nest building and incentive motivation. Also, unconditioned anxiety, perseveration, and motor impulsivity were unaltered. However, in the cognitive domain, CD2-knockouts showed reduced executive function in assays of rule-shift and rule-reversal learning, but also an impairment in working memory, that was resistant against LY379268. In contrast, sustained attention and forms of spatial and object-related memory that are mediated by short-term habituation of stimulus-specific attention were intact. Our results suggest, that CD2-KO mice are a valuable model in translational research targeted at the pharmacoresistant cognitive symptom domain in causal relation to hippocampal over-activity in the prodrome-to-psychosis transition.

animal behavior and cognition↗