Biology subjects

Gorin, A.

Publications and source records attributed to Gorin, A..

3 recordsLinked to original sources

bioRxiv2025

IFNγ-induced memory in human macrophages is not sustained by epigenetic changes but the durability of the cytokine itself

Macrophages, as key sentinel cells of the innate immune system, can retain memory of prior stimulus exposure. Interferon gamma (IFN{gamma}) plays a central role in maintaining trained immunity in vivo and can induce potent memory in macrophages. Such memory is associated with the formation of de novo enhancers that alter gene expression responses to subsequent stimuli. However, how such enhancers are maintained after cytokine exposure remains unclear. We report that durable IFN{gamma}-induced enhancers can last for days after cytokine washout, yet the underlying persistence mechanism is not cell-intrinsic. IFN{gamma}-treated macrophages continue to exhibit JAK/STAT signaling days after cytokine removal. Blocking IFN{gamma} signaling with a JAK inhibitor or anti-IFN{gamma} neutralizing antibodies after cytokine removal is sufficient to reverse IFN{gamma}-induced enhancers and erase the potentiated state of the treated macrophages. Our findings suggest that epigenetic changes in macrophages do not inherently encode innate immune memory or a "potentiated" macrophage state, but in fact are themselves dependent on ongoing cytokine signaling. These findings suggest new possibilities for pharmacologic interventions to reverse aberrantly trained immune states associated with pathology.

immunology↗

bioRxiv2022

Ambiguous tDCS: transcranial direct current stimulation effects on performance of monetary incentive delay task reinforcement learning

Transcranial electrical stimulation (tES) serves as a powerful technique for assessing the causal role of specific brain regions in behavior, including decision-making. While tES studies investigating sensorimotor function yield unequivocal results, cognitive research reveals considerable ambiguity and diversity in stimulation-related effects. The consequences of transcranial direct current stimulation (tDCS) on cognitive functioning are not consistently predictable based on the current direction (cathodal or anodal), which limits its applicability in cognitive research. In the present study, we further explored tES effect ambiguity in cognitive tasks by modulating medial frontal cortex (MFC) activity in an auditory monetary incentive delay (MID) task, where participants responded to acoustic cues encoding expected monetary losses using cathodal tDCS. We analyzed feedback-related negativity (FRN), reflecting prediction error processing when participants encountered losses compared to no losses during two subsequent MID task sessions, and exogenous P2 response to stimulus onset unrelated to anticipated monetary incentives. We anticipated an inhibitory cathodal tDCS effect on both P2 response and FRN. Contrary to our expectations, we observed a facilitatory effect of cathodal tDCS on FRN, replicating our earlier results (Gorin et al., 2022). No effect of stimulation was observed on P2; however, tDCS influenced the learning effect of P2. The difference in P2 amplitude between the first and second sessions, observed in the sham group, was absent in the group that received cathodal tDCS. We offered the interpretation of the complex picture of tES effects during auditory MID performance in light of brain plasticity theory for P2 and reward-learning mechanisms for FRN. Importantly, our findings regarding the multidirectionality of tDCS effects on cognitive function challenge the utility of tES as a readily employable method for testing brain causality in highly complex neurocognitive events, such as decision-making.

neuroscience↗

bioRxiv2016

RL mechanisms of short-term plasticity of auditory cortex

The decision-making process is exposed to modulatory factors, and, according to the expected value (EV) concept the two most influential factors are magnitude of prospective behavioural outcome and probability of receiving this outcome. The discrepancy between received and predicted outcomes is reflected by the reward prediction error (RPE), which is believed to play a crucial role in learning in dynamic environment. Feedback related negativity (FRN), a frontocentral negative component registered in EEG during feedback presentation, has been suggested as a neural signature of RPE. In modern neurobiological models of decision-making the primary sensory input is assumed to be constant over the time and independent of the evaluation of the option associated to it. In this study we investigated whether the electrophysiological changes in auditory cues perception is modulated by the strengths of reinforcement signal, represented in the EEG as FRN.\n\nWe quantified the changes in sensory processing through a classical passive oddball paradigm before and after performance a neuroeconomic monetary incentive delay (MID) task. Outcome magnitude and probability were encoded in the physical characteristics of auditory incentive cues. We evaluated the association between individual biomarkers of reinforcement signal (FRN) and the degree of perceptual learning, reflected by changes in auditory ERP components (mismatch negativity and P3a). We observed a significant correlation of MMN and valence - dFRN, reflecting differential processing of gains and omission of gains. Changes in P3a were correlated to probability - dFRN, including information on salience of the outcome, in addition to its valence.\n\nMID task performance evokes plastic changes associated with more fine-grained discrimination of auditory anticipatory cues and enhanced involuntary attention switch towards these cues. Observed signatures of neuro-plasticity of the auditory cortex may play an important role in learning and decision-making processes through facilitation of perceptual discrimination of valuable external stimuli. Thus, the sensory processing of options and the evaluation of options are not independent as implicitly assumed by the modern neuroeconomics models of decision-making.

neuroscience↗