Electrophysiology of Dendritic Spines: Information Processing, Dynamic Compartmentalization, and Synaptic Plasticity.

For many years, synaptic transmission was considered as information transfer between presynaptic neuron and postsynaptic cell. At the synaptic level, it was thought that dendritic arbors were only receiving and integrating all information flow sent along to the soma, while axons were primarily responsible for point-to-point information transfer. However, it is important to highlight that dendritic spines play a crucial role as postsynaptic components in central nervous system (CNS) synapses, not only integrating and filtering signals to the soma but also facilitating diverse connections with axons from many different sources. The majority of excitatory connections from presynaptic axonal terminals occurs on postsynaptic spines, although a subset of GABAergic synapses also targets spine heads. Several studies have shown the vast heterogeneous morphological, biochemical, and functional features of dendritic spines related to synaptic processing. In this chapter (adding to the relevant data on the biophysics of spines described in Chap. 1 of this book), we address the up-to-date functional dendritic characteristics assessed through electrophysiological approaches, including backpropagating action potentials (bAPs) and synaptic potentials mediated in dendritic and spine compartmentalization, as well as describing the temporal and spatial dynamics of glutamate receptors in the spines related to synaptic plasticity.

Cell therapy for neurological disorders: Progress towards an embryonic medial ganglionic eminence progenitor-based treatment.

Impairment of development, migration, or function of inhibitory interneurons are key features of numerous circuit-based neurological disorders, such as epilepsy. From a therapeutic perspective, symptomatic treatment of these disorders often relies upon drugs or deep brain stimulation approaches to provide a general enhancement of GABA-mediated inhibition. A more effective strategy to target these pathological circuits and potentially provide true disease-modifying therapy, would be to selectively add new inhibitory interneurons into these circuits. One such strategy, using embryonic medial ganglionic (MGE) progenitor cells as a source of a unique sub-population of interneurons, has already proven effective as a cell transplantation therapy in a variety of preclinical models of neurological disorders, especially in mouse models of acquired epilepsy. Here we will discuss the evolution of this interneuron-based transplantation therapy in acquired epilepsy models, with an emphasis on the recent adaptation of MGE progenitor cells for xenotransplantation into larger mammals.

GABAergic synaptic transmission and cortical oscillation patterns in the primary somatosensory area of a valproic acid rat model of autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction associated with repetitive or stereotyped behaviour. Prenatal valproic acid (VPA) exposure in rodents is a commonly used model of ASD. Resveratrol (RSV) has been shown to prevent interneuronal and behavioural impairments in the VPA model. We investigated the effects of prenatal VPA exposure and RSV on the GABAergic synaptic transmission, brain oscillations and on the genic expression of interneuron-associated transcription factor LHX6 in the primary somatosensory area (PSSA). Prenatal VPA exposure decreased the sIPSC and mIPSC frequencies and the sIPSC decay kinetics onto layers 4/5 pyramidal cells of PSSA. About 40% of VPA animals exhibited absence-like spike-wave discharge (SWD) events associated with behaviour arrest and increased power spectrum density of delta, beta and gamma cortical oscillations. VPA animals had reduced LHX6 expression in PSSA, but VPA animals treated with RSV had no changes on synaptic inhibition or LHX6 expression in the PSSA. SWD events associated with behaviour arrest and the abnormal increment of cortical oscillations were also absent in VPA animals treated with RSV. These findings provide new venues to investigate the role of both RSV and VPA in the pathophysiology of ASD and highlight the VPA animal model as an interesting tool to investigate pathways related to the aetiology and possible future therapies to this neuropsychiatric disorder.

In vitro Oscillation Patterns Throughout the Hippocampal Formation in a Rodent Model of Epilepsy.

Specific oscillatory patterns are considered biomarkers of pathological neuronal network in brain diseases, such as epilepsy. However, the dynamics of underlying oscillations during the epileptogenesis throughout the hippocampal formation in the temporal lobe epilepsy is not clear. Here, we characterized in vitro oscillatory patterns within the hippocampal formation of epileptic rats, under 4-aminopyridine (4-AP)-induced hyperexcitability and during the spontaneous network activity, at two periods of epileptogenesis. First, at the beginning of epileptic chronic phase, 30 days post-pilocarpine-induced Status Epilepticus (SE). Second, at the established epilepsy, 60 days post-SE. The 4-AP-bathed slices from epileptic rats had increased susceptibility to ictogenesis in CA1 at 30 days post-SE, and in entorhinal cortex and dentate gyrus at 60 days post-SE. Higher power and phase coherence were detected mainly for gamma and/or high frequency oscillations (HFOs), in a region- and stage-specific manner. Interestingly, under spontaneous network activity, even without 4-AP-induced hyperexcitability, slices from epileptic animals already exhibited higher power of gamma and HFOs in different areas of hippocampal formation at both periods of epileptogenesis, and higher phase coherence in fast ripples at 60 days post-SE. These findings reinforce the critical role of gamma and HFOs in each one of the hippocampal formation areas during ongoing neuropathological processes, tuning the neuronal network to epilepsy.

GABAergic interneurons in epilepsy: More than a simple change in inhibition.

The pathophysiology of epilepsy has been historically grounded on hyperexcitability attributed to the oversimplified imbalance between excitation (E) and inhibition (I) in the brain. The decreased inhibition is mostly attributed to deficits in gamma-aminobutyric acid-containing (GABAergic) interneurons, the main source of inhibition in the central nervous system. However, the cell diversity, the wide range of spatiotemporal connectivity, and the distinct effects of the neurotransmitter GABA especially during development, must be considered to critically revisit the concept of hyperexcitability caused by decreased inhibition as a key characteristic in the development of epilepsy. Here, we will discuss that behind this known mechanism, there is a heterogeneity of GABAergic interneurons with distinct functions and sources, which have specific roles in controlling the neural network activity within the recruited microcircuit and altered network during the epileptogenic process. This article is part of the Special Issue "NEWroscience 2018.