Biology subjects

Niedringhaus, M.

Publications and source records attributed to Niedringhaus, M..

3 recordsLinked to original sources

bioRxiv2025

Aberrant medial prefrontal cortex activity and flexible behavior in the TgF344-AD rat model of Alzheimer's disease

Cognitive deficits, including deficits in the ability to shift behavior following negative consequences, often precede the accumulation of canonical neuropathological markers (A{beta} plaques and tauopathy) and severe dementia in Alzheimers disease (AD) patients. The Tg-F344-AD rat model exhibits age-dependent AD pathology and memory deficits that recapitulate AD, However, it is unknown how medial prefrontal cortex activity is altered in awake and behaving AD rats during learning and/or flexible behavior. Here we determine the ability of in 6-7month-old TgF344-AD rats to learn reward predictive cues and to shift behavior away from reward-predictive cues following outcome devaluation while recording mPFC neurons. Specifically, AD rats (n=17) and wild-type littermates (n=17) were presented with two distinct cues as conditioned stimuli (CS+) predicting distinct outcomes. A conditioned taste aversion to one outcome was induced, after which the rats were tested post-devaluation to evaluate their ability to avoid the CS+ associated with the devalued outcome. We found a loss of motivated behavior during learning and a loss of flexible behavior during testing in 6-7-month-old AD rats relative to WT littermate controls. In addition, there was differential aberrant mPFC encoding of cue-outcome associations in AD rats during conditioning and following outcome devaluation. Specifically, AD animals show fewer neurons during conditioning that encode both the cue and the outcome than WT animals. Also, AD animals also showed a greater proportion of neurons that exhibited an excited response to reward predictive cues post-outcome devaluation. Together, these data contribute to our understanding of alterations in mPFC that may underline prodromal AD behavioral deficits to inform future treatments.

neuroscience↗

bioRxiv2024

Medial prefrontal cortex and nucleus reuniens are critical for working memory in an operant delayed nonmatch task

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. The prefrontal cortex and its connections with thalamic subregions are thought to mediate specific aspects of working memory, including engaging with the hippocampus to mediate memory retrieval. We used an operant delayed-non match to position task, which does not require the hippocampus, to determine roles of the rodent medial prefrontal cortex (mPFC), the nucleus reuniens thalamic region (RE), and their connection. We found that transient inactivation of the mPFC and RE using the GABA-A agonist muscimol led to a delay-independent reduction in behavioral performance in the delayed non-match to position paradigm. Critically, we used a chemogenetic approach to determine the directionality of the necessary circuitry for behavioral performance reliant on working memory. Specifically, when we targeted mPFC neurons that project to the RE (mPFC-RE) we found a delay- independent reduction in the delayed non-match to position task, but not when we targeted RE neurons that project to the mPFC (RE-mPFC). Our results suggest a broader role for the mPFC-RE circuit in mediating working memory beyond the connection with the hippocampus.

neuroscience↗

bioRxiv2022

Prelimbic cortex neural encoding dynamically tracks expected outcome value

Animals must modify their behavior based on updated expected outcomes in a changing environment. Prelimbic cortex (PrL) neural encoding during learning predicts and is necessary for appropriately altering behavior based on new expected outcome value following devaluation. We aimed to determine how PrL neural activity encodes reward predictive cues after the expected outcome value of those cues is decreased following conditioned taste aversion. In one post- devaluation session, rats were tested under extinction to determine their ability alter their behavior to the expected outcome values (i.e., extinction test). In a second post-devaluation session, rats were tested with the newly devalued outcome delivered so that the rats experienced the updated outcome value within the session (i.e., re-exposure test). We found that PrL neural encoding to the cue associated with the devalued reward predicted the ability of rats to suppress behavior in the extinction test session, but not in the re-exposure test session. While all rats were able to successfully devalue the outcome during conditioned taste aversion, a subset of rats continued to consume the devalued outcome in the re-exposure test session. We found differential patterns of PrL neural encoding in the population of rats that did not avoid the devalued outcome during the re-exposure test compared to the rats that successfully avoided the devalued outcome. Our findings suggest that PrL neural encoding dynamically tracks expected outcome values, and differential neural encoding in the PrL to reward predictive cues following expected outcome value changes may contribute to distinct behavioral phenotypes.

neuroscience↗