An ultra-short-acting benzodiazepine in thalamic nucleus reuniens undermines fear extinction via intermediation of hippocamposeptal circuits.

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

Memory Trace for Fear Extinction: Fragile yet Reinforceable.

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement, allowing the organism to re-adapt to ever-changing situations. Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory, this new memory is more readily forgettable than the original fear memory. The brain's cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear. Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory. In this review, we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction, aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

[Diagnosis and treatment of Lophomonas blattarum infection in 26 patients with bacterial pneumonia].

The clinical features of Lophomonas blattarum infection in 26 patients with bacterial pneumonia were analyzed. Common manifestation included fever, cough and breathlessness. Computed tomography (CT) showed interstitial change and alveolar exudation. The parasites were found in sputum smear and from the bronchoalveolar lavage fluid (BALF). Metronidazole was effectively used to cure the pulmonary infection of L. blattarum.