Biology subjects

Griego, E.

Publications and source records attributed to Griego, E..

3 recordsLinked to original sources

bioRxiv2025

Layer V Neocortical Neurons From Individuals With Drug-Resistant Epilepsy Show Multiple Synaptic Alterations but Lack Somatic Hyperexcitability

Although neuronal hyperexcitability is the primary mechanism underlying seizure activity in epilepsy, little is known about how different neuronal mechanisms at different organizational levels contribute to network hyperexcitability in the human epileptic brain. In this study, we determined a series of cellular and synaptic properties of layer V pyramidal neurons from neocortical tissue of patients with drug-resistant epilepsy that may contribute the hyperexcitable state associated with epilepsy. Using the whole cell, patch-clamp technique, and extracellular recordings, we determined the passive and active electrophysiological properties of layer V pyramidal neurons with regular spiking phenotypes from temporal, parietal, and frontal neocortices surgically resected from individuals with drug-resistant epilepsy. Also, the glutamatergic strength, the synchronicity between presynaptic volleys and field excitatory postsynaptic potentials, and short-term, frequency-dependent plasticity were determined at the synaptic level. Lastly, biocytin-filled pyramidal neurons were used to perform post hoc digital reconstructions and morphometric analyses. The collected data revealed that pyramidal neurons exhibit minimal spontaneous activity, similar resting membrane potentials, and input resistance values among the temporal, parietal, and frontal neocortices. Although frontal neurons were more hyperexcitable than temporal and parietal neurons, the firing output was comparable to that previously observed in non-pathological human tissue. The digital reconstructions confirmed the identity of pyramidal neurons and revealed alterations in dendritic complexity. In contrast, the analyses of the extracellular recordings uncovered significant desynchronization between presynaptic excitability and postsynaptic activity and loss of short-term depression in response to repetitive stimulation within the gamma range (30 Hz). Our data suggest that neocortical layer V pyramidal neurons from individuals with drug-resistant epilepsy are not necessarily hyperexcitable at the somatic level. Instead, synaptic alterations, such as synaptic desynchronization and a loss of frequency-dependent short-term depression may significantly contribute to the hyperexcitable state observed during seizure activity.

neuroscience↗

bioRxiv2024

Maternal Immune Activation Alters Temporal Precision of Spike Generation of CA1 Pyramidal Neurons by Unbalancing GABAergic Inhibition in the Offspring

Maternal immune activation (MIA) represents a risk factor for neuropsychiatric disorders associated with neurodevelopmental alterations. A growing body of evidence from rodents and non-human primates shows that MIA induced by viral or bacterial infections results in several neurobiological alterations in the offspring. These changes may play an important role in the pathophysiology of psychiatric disorders like schizophrenia and autism spectrum disorders, whose clinical features include impairments in cognitive processing and social performance. Such alterations are causally associated with the maternal inflammatory response to infection rather than with the infection itself. Previously, we reported that CA1 pyramidal neurons of mice exposed to MIA exhibit increased excitability accompanied by a reduction in dendritic complexity. However, potential alterations in cellular and synaptic rules that shape the neuronal computational properties of the offspring remain to be determined. In this study, using mice as subjects, we identified a series of cellular and synaptic alterations endured by CA1 pyramidal neurons of the dorsal hippocampus in a lipopolysaccharide-induced MIA model. Our data provide evidence that MIA reshapes the excitation-inhibition balance by decreasing the perisomatic GABAergic inhibition impinging on CA1 pyramidal neurons. These alterations yield a dysregulated amplification of the temporal and spatial synaptic integration. In addition, MIA-exposed offspring displayed social and anxiety-like abnormalities. Collectively, these findings contribute to the understanding of the cellular and synaptic alterations underlying the behavioral symptoms present in neurodevelopmental disorders associated with MIA. HighlightsO_LILPS injection during pregnancy (MIA) increases cytokine production and decreases litter size. C_LIO_LIMIA increases the temporal summation of EPSPs in hippocampal neurons. C_LIO_LIMIA alters spatial summation and increases the probability of action potential discharge. C_LIO_LIMIA alters the inhibitory/excitatory balance of CA1 pyramidal cells. C_LIO_LIMIA alters the expression of GAD-positive interneurons. C_LIO_LIMIA alters the performance of several behavioral tests in offspring. C_LI

neuroscience↗

bioRxiv2024

BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the livers production of ketone bodies, primarily {beta}-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200M) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and {omega}-3 docosahexaenoic acid (200M), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.

neuroscience↗