Biology subjects

Prizon, T.

Publications and source records attributed to Prizon, T..

3 recordsLinked to original sources

bioRxiv2023

Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress

Stress-related neuropsychiatric disorders are complex conditions that are difficult to diagnose and treat due to the variety of symptoms they present with. While animal models have been instrumental in understanding their underlying mechanisms, there is an ongoing debate about the validity of behavioral measures to address specific disorders. Here, we conducted an extensive ethological characterization of behavioral variables associated with anxiety and depression and employed a multidimensional approach to investigate stress susceptibility in male Wistar rats. The rats underwent inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests over several days. Our study identified phenotypically distinct clusters, including fully characterized stress-susceptible and stress-resilient subpopulations, along with intermediate phenotypes. Reduced time in elevated plus maze open arms, diminished sucrose preference and increased escape failures consistently differentiated susceptible from resilient rats. Behavior in the forced swim test was unrelated to stress susceptibility. In conclusion, our study sheds light on the relationships between classical behavioral measures in animal models of depression, highlighting distinct patterns that differentiate susceptibility from resilience. It emphasizes the importance of a multidimensional assessment of behavioral responses in animal models for a better understanding of stress-related neuropsychiatric disorders. HIGHLIGHTSO_LIClustering of features reveals a correlation pattern that separates behavioral variables associated with susceptibility from those associated with resilience to stress C_LIO_LIMultidimensional patterns of covariation among behavioral measures distinguish helpless from non-helpless individuals and indicate independence from forced swim test behavior. C_LIO_LIClustering of individuals discriminates stressed subjects and reveals multidimensional behavioral phenotypes of resilience and susceptibility, indicating different stress-coping strategies. C_LI

animal behavior and cognition↗

bioRxiv2022

Dysfunctional Hippocampal-Prefrontal Connectivity without Neuronal Loss Is Associated with Psychotic-Like Behaviors Following Early-Life Seizure

Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common link between such disorders. However, the mechanisms underlying these outcomes and how they relate to specific behavioral alterations are unclear. We hypothesized that specific dysfunctions of hippocampal-cortical communication due to early-life seizure would be associated with distinct behavioral alterations observed in adulthood. Here, we performed a multilevel study to investigate behavioral, electrophysiological, histopathological, and neurochemical long-term consequences of early-life Status epilepticus in male rats. We show that adult animals submitted to early-life seizure (ELS) present working memory impairments and sensorimotor disturbances, such as hyperlocomotion, poor sensorimotor gating, and sensitivity to psychostimulants despite not exhibiting neuronal loss. Surprisingly, cognitive deficits were linked to an aberrant increase in the HPC-PFC long-term potentiation (LTP) in a U-shaped manner, while sensorimotor alterations were associated with heightened neuroinflammation, as verified by glial fibrillary acidic protein (GFAP) expression, and altered dopamine neurotransmission. Furthermore, ELS rats displayed impaired HPC-PFC theta-gamma coordination and an abnormal brain state during active behavior resembling rapid eye movement (REM) sleep oscillatory dynamics. Our results point to impaired HPC- PFC functional connectivity as a possible pathophysiological mechanism by which ELS can cause cognitive deficits and psychiatric-like manifestations even without neuronal loss, bearing translational implications for understanding the spectrum of multidimensional developmental disorders linked to early-life seizures.

neuroscience↗

bioRxiv2022

Decoding Fear or Safety and Approach or Avoidance by Brain-Wide Network Dynamics

Discerning safety from threat and positive or negative outcomes of adversity are fundamental for mental health. Many brain structures have been implicated in both adaptive and maladaptive stress coping, however, how multiple regions function together as a network in the processing of this information is unclear. Here, we recorded local field potentials from seven regions of the mesolimbic-hippocampal-prefrontal cortical network (MLHFC) of male rats during the conditioning of a stimulus (CS) to the absence (safety) and then to the anticipation (fear) of footshocks, and during an approach-avoidance task. We developed a machine learning pipeline to investigate the relevance of specific features of oscillatory activity in the decoding of fear versus safety and approach versus avoidance. We found that decoding performance increased as a function of the number of brain regions included, reaching the best classification if all regions were considered. In addition, the best decoding was obtained from frequencies within the theta range (4-10 Hz). Remarkably, decoder models showed robust generalization within but not between individuals. Nevertheless, we were also able to identify patterns of MLHFC activity that decoded stress coping states from all rats. These patterns were characterized by increased brain-wide theta synchrony during fear and preceding approach. Our results indicate that stress coping information is encoded at the brain-wide level and highlight individual variability in this neural processing. Our findings also suggest that MLHFC network theta activity underlies active stress coping with both aversive and positive motivational valences. SIGNIFICANCE STATEMENTThe appraisal of safety versus threat and positive versus negative valence of adversity are core dimensions of emotional experience and stress coping. We developed a new behavioral protocol that discriminates states of fear, safety, approach, and avoidance in a single subject and a machine learning-based method to investigate how neural oscillations can decode such states. Our work provides evidence that stress coping is processed at multiple regions on a brain-wide level involving network oscillations at the theta frequencies, which especially synchronizes during fear and approach. We highlight the potentials of combining artificial intelligence and multi-site electroencephalography to guide therapeutic decisions in precision psychiatry and theta-boosting stimulation therapies for stress-related disorders, especially related to cognitive and motivational deficits.

neuroscience↗