Vol 111, No 4 (2025)

In the CNS, glutamate is the main excitatory neurotransmitter, while gamma-aminobutyric acid (GABA) functions as the main inhibitory neurotransmitter. N-acetylaspartylglutamate (NAAG), in turn, is the most abundant neuropeptide in the CNS and is also capable of acting as a neurotransmitter. This review analyzes experimental data proving the participation of all three of these signaling molecules in the functioning of the neuromuscular junction, which is a “classical” cholinergic synapse of the peripheral nervous system and, until recently, was considered the most studied synaptic junction in the organism of vertebrates and humans. To date, all three signaling molecules have been identified in the area of the neuromuscular junction, data have been obtained on their release into the synaptic cleft, and receptor proteins have been discovered whose activation affects the processes of both spontaneous and evoked quantal release of acetylcholine. It is noted that in mammalian synapses, glutamate, NAAG and GABA unidirectionally inhibit the process of non-quantal release of acetylcholine. The mechanisms of these modulatory pathways of glutamate and its derivatives signaling are realized with the involvement of all three compartments of the synaptic contact: nerve ending, muscle fiber and perisynaptic Schwann cell.

Febrile seizures (FS) in early childhood can lead to the development of epilepsy; however, in most cases, they resolve without consequences. The neurophysiological mechanisms that protect the brain from the effects of FS remain poorly understood. It is also known that the risk of epilepsy significantly increases if a child has congenital abnormalities in the structure of the cerebral cortex. In this study, we examined functional changes in the hippocampus of young rats subjected to FS on the 10th postnatal day (P10) with freezing-induced focal cortical dysplasia (FCD) on P0. Experiments were conducted on three groups of animals: 1) control group (Ctrl) – rats without FS and FCD; 2) FS group – rats subjected to hyperthermia-induced FS on P10; 3) FS+FCD group – rats with cortical freezing on P0 and FS on P10. Using recordings of local synaptic potentials in the CA1 region of the hippocampus, we found that FS led to significant changes in synaptic transmission. In the FS group, there was an increase in the threshold for population spike generation, a decrease in the synaptic transmission efficacy ratio, and an increase in the paired-pulse ratio. These changes indicate reduced activity of CA3-CA1 glutamatergic synapses, which may represent a compensatory response preventing epileptogenesis. However, in the FS+FCD group, such compensatory changes were absent: synaptic transmission parameters did not differ from those in the control group. This suggests that FCD impedes the activation of protective mechanisms in the hippocampus in response to FS. Thus, the presence of cortical dysplasia may increase the risk of epilepsy following FS by 20 blocking natural compensatory processes. Our results highlight the importance of studying the interaction between congenital cortical developmental abnormalities and the consequences of FS for understanding the mechanisms of epileptogenesis.

The aim of this study was to investigate the functional role of the TAAR1 receptor, one of the representatives of trace amine-associated receptors (TAARs). The behavior of TAAR1-KO knockout mice and wild-type WT mice were studied in tests reflecting the anxiety and depressive-like conditions. In the Novelty-Suppressed Feeding Test, it was shown that in TAAR1-KO mice the average time to approach the bait was significantly shorter than in WT mice. No statistically significant differences were found for all other parameters of feeding behavior (latency before the start of eating, duration of food consumption, number of approaches with sniffing the bait, number of meals). In the tail suspension test and the Porsolt forced swimming test, the LP of the first immobilization was significantly higher in TAAR1-KO mice. In the Porsolt test, TAAR1-KO mice showed a lower duration of immobilization compared to WT mice.