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Nahmoud, I.

Publications and source records attributed to Nahmoud, I..

3 recordsLinked to original sources

PV - Oligodendrocyte Interactions in the Infralimbic Cortex Promote Extracellular Plasticity after Safety Learning

Safety learning is mediated by the infralimbic region (IL) of the medial prefrontal cortex, but its cellular mechanisms are poorly understood. Here we show that safety learning improves cognitive flexibility in the long-term, which is associated with recruitment of oligodendrocyte progenitor cells to a satellite position at parvalbumin (PV) interneurons in the IL and their maturation into oligodendrocytes (OLs), as well as a decrease in perineuronal nets (PNNs) surrounding PVs paired with satellite OLs. Using scRNA transcriptomic data mining, we demonstrate that immature OLs primarily express PNN assembly genes, whereas mature OLs express PNN degradation enzymes. We then demonstrate that inhibiting IL PVs during safety learning prevents safety-induced cognitive flexibility, satellite OL maturation, and PNN degradation around IL PV. Thus, we propose that safety learning drives a novel form of neuro-glial plasticity that helps degrade PNNs around PV interneurons via OL recruitment and maturation, thereby shaping IL long-term activity.

neuroscience↗

Prelimbic-dependent activation of amygdala somatostatin interneurons signals non-aversive cues to promote discrimination.

The amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues, when they block sensory-evoked phase resetting of theta-oscillations. Further, we show that SOM activation is PL-dependent, and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.

neuroscience↗

Salient Safety Conditioning Improves Novel Discrimination Learning

Generalized fear is one purported mechanism of anxiety that is a target of clinical and basic research. Impaired fear discrimination has been primarily examined from the perspective of increased fear learning, rather than how learning about non-threatening stimuli affects fear discrimination. To address this question, we tested how three Safety Conditioning protocols with varied levels of salience allocated to the safety cue compared to classic Fear Conditioning in their impact on subsequent innate anxiety, and differential fear learning of new aversive and neutral cues. Using a high anxiety strain of mice (129SvEv, Taconic), we show that Fear Conditioned animals show little exploration of the anxiogenic center of an open field 24 hours later, and poor discrimination during new differential conditioning 7 days later. Three groups of mice underwent Safety Conditioning, (i) the safety tone was unpaired with a shock, (ii) the safety tone was unpaired with the shock and co-terminated with a house light signaling the end of the safety period, and (iii) the safety tone was unpaired with the shock and its beginning co-occurred with a house light, signaling the start of a safety period. Mice from all Safety Conditioning groups showed higher levels of open field exploration than the Fear Conditioned mice 24 hours after training. Furthermore, Safety Conditioned animals showed improved discrimination learning of a novel non-threat, with the Salient Beginning safety conditioned group performing best. These findings indicate that high anxiety animals benefit from salient safety training to improve exploration and discrimination of new non-threating stimuli. Highlights O_LISafety training using salient cues improves safety learning in high anxiety mice C_LIO_LISalient Safety training improves novel fear discrimination learning C_LIO_LISafety training improves exploration in a novel anxiogenic environment C_LI

neuroscience↗