Biology subjects

Zacharias, L. R.

Publications and source records attributed to Zacharias, L. R..

3 recordsLinked to original sources

bioRxiv2025

Single electrically induced epileptic afterdischarge triggers synaptic weakening, AMPA receptor endocytosis and shrinkage of dendritic spines in the hippocampus

Afterdischarge (AD) is an experimental model of electrically induced seizures. When induced in limbic structures, AD is known to induce acute behavioral alterations and flattening of local field potentials that persist for a few minutes. However, impairments in more complex cognitive processes such as learning and memory, can last for hours after the seizure. Considering the mismatch between ephemeral postictal electrophysiological changes and long-lasting cognitive impairments, synaptic plasticity emerges as a possible mechanism that integrates these findings. Therefore, we used a multilevel approach to evaluate the effects of a single seizure on synaptic plasticity. First, we showed that a single AD-eliciting stimulation at the perforant pathway-dentate gyrus (PP-DG) synapse causes long-lasting decrease of evoked postsynaptic potentials. Then, we observed that this functional alteration was accompanied by shrinkage of mushroom-shaped spines in the DG. Lastly, reduced levels of p(Ser845)-GluA1 and GluA1 subunits of AMPA receptors (AMPARs) were found in the hippocampal postsynaptic density. Together, our data suggest that a seizure induces a long-term depression (LTD)-like synaptic plasticity phenomenon, which is characterized by synaptic weakening, AMPAR endocytosis, and dendritic spines shrinkage. Furthermore, the postictal changes in synaptic plasticity observed here align with the course of cognitive impairments often reported in other studies.

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↗

bioRxiv2020

Network asynchrony underlying increased broadband gamma power

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike "contamination") affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor.

neuroscience↗