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Parvalbumin-expressing (PV+) interneurons play a key role in the maturation and synchronization of cortical circuitry and alterations in these inhibitory neurons, especially in the medial prefrontal cortex (mPFC), have been found in different psychiatric disorders. The formation of perineuronal nets (PNNs) around many of these interneurons at the end of the critical periods reduces their plasticity and sets their connectivity. Consequently, the presence of PNNs must have an important impact on the synaptic input and the physiology of PV + cells. In the present study, we have found that in adult male mice, prefrontocortical PV+ cells surrounded by PNNs show higher density of perisomatic excitatory and inhibitory puncta, longer axonal initial segments (AISs), and higher PV expression when compared with PV+ cells lacking PNNs. In order to better understand the impact of PNNs on the connectivity and physiology of PV+ interneurons in the mPFC, we have digested enzymatically these structures and have found a decrease in the density of inhibitory puncta on their perisomatic region but not on the PV+ perisomatic puncta on pyramidal neurons. Moreover, extracellular recordings show that the digestion of PNNs induces a decrease in y activity, an oscillation dependent on PV+ cells, in the mPFC of anesthetized mice. Our results suggest that the presence of PNNs enwrapping PV+ cells regulates their inhibitory input and has a potent influence on their activity. These results may be relevant for psychiatric research, given the alterations in PNNs, PV+ interneurons and their physiology described in different mental disorders. [ABSTRACT FROM AUTHOR]

The epileptogenic focus is a brain area that may be surgically removed to control of epileptic seizures. Locating it is an essential and crucial step prior to the surgical treatment. However, given the difficulty of determining the localization of this brain region responsible of the initial seizure discharge, many works have proposed machine learning methods for the automatic classification of focal and non-focal electroencephalographic (EEG) signals. These works use automatic classification as an analysis tool for helping neurosurgeons to identify focal areas off-line, out of surgery, during the processing of the huge amount of information collected during several days of patient monitoring. In turn, this paper proposes an automatic classification procedure capable of assisting neurosurgeons online, during the resective epilepsy surgery, to refine the localization of the epileptogenic area to be resected, if they have doubts. This goal requires a real-time implementation with as low a computational cost as possible. For that reason, this work proposes both a feature set and a classifier model that minimizes the computational load while preserving the classification accuracy at 95.5%, a level similar to previous works. In addition, the classification procedure has been implemented on a FPGA device to determine its resource needs and throughput. Thus, it can be concluded that such a device can embed the whole classification process, from accepting raw signals to the delivery of the classification results in a cost-effective Xilinx Spartan-6 FPGA device. This real-time implementation begins providing results after a 5 s latency, and later, can deliver floating-point classification results at 3.5 Hz rate, using overlapped time-windows. [ABSTRACT FROM AUTHOR]

Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD. [ABSTRACT FROM AUTHOR]

There is evidence that Deep Brain Stimulation (DBS) produces health benefits in patients even before initiating stimulation. Furthermore, DBS electrode insertion in rat infralimbic cortex (ILC) provokes antidepressant-like effects before stimulation, due to local inflammation and astrogliosis. Consequently, a significant effect of implanting electrodes is suspected. External fields, similar in magnitude to the brain's endogenous fields, induce electric dipoles in conducting materials, in turn influencing neural cell growth through wireless effects. To elucidate if such dipoles influence depressive-like behavior, without external stimulation, the comparative effect of conducting and insulated electrodes along with the glial response is studied in unstressed rats. Naïve and implanted rats with electrically insulated or uninsulated steel electrodes were evaluated in the modified forced swimming test and expression of ILC-glial markers was assessed. An antidepressant-like effect was observed with conducting but not with insulated electrodes. Gliosis was detected in both groups, but astroglial reactivity was larger near uninsulated electrodes. Thus, induced dipoles and antidepressant-like effects were only observed with conducting implants. Such correlation suggests that dipoles induced in electrodes by endogenous fields in turn induce neuron stimulation in a feedback loop between electrodes and neural system. Further research of the effects of unwired conducting implants could open new approaches to regulating neuronal function, and possibly treat neurological disorders. [ABSTRACT FROM AUTHOR]

Severe psychiatric illnesses, for instance schizophrenia, and affective diseases or autism spectrum disorders, have been associated with cognitive impairment and perturbed excitatory-inhibitory balance in the brain. Effects in juvenile mice can elucidate how erythropoietin (EPO) might aid in rectifying hippocampal transcriptional networks and synaptic structures of pyramidal lineages, conceivably explaining mitigation of neuropsychiatric diseases. An imminent conundrum is how EPO restores synapses by involving interneurons. By analyzing ~12,000 single-nuclei transcriptomic data, we generated a comprehensive molecular atlas of hippocampal interneurons, resolved into 15 interneuron subtypes. Next, we studied molecular alterations upon recombinant human (rh)EPO and saw that gene expression changes relate to synaptic structure, trans-synaptic signaling and intracellular catabolic pathways. Putative ligand-receptor interactions between pyramidal and inhibitory neurons, regulating synaptogenesis, are altered upon rhEPO. An array of in/ex vivo experiments confirms that specific interneuronal populations exhibit reduced dendritic complexity, synaptic connectivity, and changes in plasticity-related molecules. Metabolism and inhibitory potential of interneuron subgroups are compromised, leading to greater excitability of pyramidal neurons. To conclude, improvement by rhEPO of neuropsychiatric phenotypes may partly owe to restrictive control over interneurons, facilitating re-connectivity and synapse development., (© 2024. The Author(s).)