A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil.

Inhibitory gamma-aminobutyric acidergic (GABAergic) neurons were identified in the dentate gyrus of seizure-sensitive (SS) and seizure-resistant (SR) gerbils by immunocytochemical localization of glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA. Increases in both the number of GAD+ somata and terminals were found in the dentate gyrus of the SS brains compared to the SR. The magnitude of the increase was positively correlated with the recorded seizure intensity. The increased number of GABAergic neurons in the dentate gyrus of SS gerbils could result in disinhibition of the granule cells, thereby allowing propagation of epileptiform activity through the hippocampus

Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review

This narrative review aims to provide an overview of the current literature on thepharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomerof ketamine, for the treatment of treatment-resistant depression (TRD). A literature searchusing Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 toJuly 2019). Product information and www.clinicaltrials.gov were also reviewed. The literaturesearch was limited to human studies published in English. PhaseI, II, and III studies ofintranasal esketamine for TRD were reviewed. About a third of patients with major depressivedisorder fail to achieve remission despite treatment with multiple antidepressants. Thisarticle examines the trials that led to the approval of esketamine in the United States, aswell as other recent studies of esketamine for TRD. The findings from limited phaseIII trialsillustrate that intranasal esketamine is effective and safe in reducing depressive symptomsand achieving clinical response in patients with TRD. The optimum duration and frequency ofuse are not fully understood. Although the nasal spray is a convenient dosage form, its use inpractice may be limited by cost and administrative regulation. While it may prove beneficialto many patients who suffer from TRD, further long-term data are required, along withcomparative trials with the R-isomer (arketamine). In the interim, care and monitoring shouldbe exercised in its use in clinical practice

A description of the GABAergic neurons and axon terminals in the motor nuclei of the cat thalamus.

The GABA neurons and their processes in the cat motor thalamic nuclei were identified and studied with glutamic acid decarboxylase (GAD) immunocytochemistry at both the light and electron microscopic levels. The three nuclei that comprise the motor thalamus, ventral anterior (VA), ventral medial (VM), and ventral lateral (VL), each displayed a characteristic distribution pattern of GAD-positive structures that was consistent with their afferent and intrinsic neuronal organization. All three thalamic nuclei displayed a population of small, GAD-positive cells the dendrites of which contained synaptic vesicles and participated in complex synaptic arrays such as serial synapses, triads, and glomeruli. Based on their ultrastructural features, these GAD-containing cells were identified as local circuit neurons. In contrast, the larger, GAD-negative cells were presumed to be the thalamocortical projection neurons. The axons of GAD-positive local circuit neurons could not be identified in these preparations. The number of GAD-positive dendrites in the neuropil was different for the three thalamic nuclei. In the VA and VM, the GAD-positive dendrites were numerous and formed symmetric synapses with dendrites of GAD-negative cells, mainly in association with corticothalamic boutons. Within VL, the GAD-containing dendrites were more numerous than in VA and VM and formed synapses at influential locations on presumed thalamocortical projection neurons, such as bases of primary dendrites, and bifurcation sites of primary and secondary dendrites. The VA and anterolateral VM nuclei that receive inhibitory GABAergic afferents from the entopeduncular nucleus and substantia nigra contained the highest concentration of large GAD-positive axon terminals. These boutons contained pleomorphic vesicles and numerous mitochondria and formed symmetric synapses and multiple puncta adherentes with dendrites and somata of presumed thalamocortical projection neurons. The size, ultrastructural features, and distribution of these GAD-positive boutons were similar to those features described for basal ganglia terminals in the motor thalamus of the cat. In addition, similar large-size GAD-positive boutons were observed in the medial VM, which receives basal ganglia afferents exclusively from the substantia nigra. The concentration of these terminals in medial VM along the dendrites of thalamocortical projection neurons was much less than that in VA and anterolateral VM. The VL nucleus which lacks basal ganglia input did not contain any large GAD-positive boutons.(ABSTRACT TRUNCATED AT 400 WORDS