Summary: As it was established that aging is not associated with massive neuronal loss, as was believed in the mid‐20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging‐related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging‐related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging‐induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases.

Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS) and glutamatergic transmission is critical for controlling neuronal activity. Glutamate is stored in synaptic vesicles and released upon stimulation. The homeostasis of glutamatergic system is maintained by a set of transporters present in plasma membrane and in the membrane of synaptic vesicles. The family of vesicular glutamate transporters in mammals is comprised of three highly homologous proteins: VGLUT1-3. The expression of particular VGLUTs is largely complementary with limited overlap and so far they are most specific markers for neurons that use glutamate as neurotransmitter. VGLUTs are regulated developmentally and determine functionally distinct populations of glutamatergic neurons. Controlling the activity of these proteins could potentially modulate the efficiency of excitatory neurotransmission. This review summarizes the recent knowledge concerning molecular and functional characteristic of vesicular glutamate transporters, their development, contribution to synaptic plasticity and their involvement in pathology of the nervous system. Correspondence should be addressed to M. Liguz-Lecznar, Email: m.liguz@nencki.gov.pl

Since its discovery over four decades ago, somatostatin receives growing scientific and clinical interest. Being localized in the nervous system in a subset of interneurons somatostatin acts as a neurotransmitter or neuromodulator and its role in the fine-tuning of neuronal activity and involvement in synaptic plasticity and memory formation are widely recognized in the recent literature. Combining transgenic animals with electrophysiological, anatomical and molecular methods allowed to characterize several subpopulations of somatostatin-containing interneurons possessing specific anatomical and physiological features engaged in controlling the output of cortical excitatory neurons. Special characteristic and connectivity of somatostatin-containing neurons set them up as significant players in shaping activity and plasticity of the nervous system. However, somatostatin is not just a marker of particular interneuronal subpopulation. Somatostatin itself acts pre- and postsynaptically, modulating excitability and neuronal responses. In the present review we combine the knowledge regarding somatostatin and somatostatin-containing interneurons, trying to incorporate it into the current view concerning the role of the somatostatinergic system in cortical plasticity.

Despite the obvious differences in the pathophysiology of distinct neuropsychiatric diseases or neurodegenerative disorders, some of them share some general but pivotal mechanisms, one of which is the disruption of excitation/inhibition balance. Such an imbalance can be generated by changes in the inhibitory system, very often mediated by somatostatin-containing interneurons (SOM-INs). In physiology, this group of inhibitory interneurons, as well as somatostatin itself, profoundly shapes the brain activity, thus influencing the behavior and plasticity; however, the changes in the number, density and activity of SOM-INs or levels of somatostatin are found throughout many neuropsychiatric and neurological conditions, both in patients and animal models. Here, we (1) briefly describe the brain somatostatinergic system, characterizing the neuropeptide somatostatin itself, its receptors and functions, as well the physiology and circuitry of SOM-INs; and (2) summarize the effects of the activity of somatostatin and SOM-INs in both physiological brain processes and pathological brain conditions, focusing primarily on learning-induced plasticity and encompassing selected neuropsychological and neurodegenerative disorders, respectively. The presented data indicate the somatostatinergic-system-mediated inhibition as a substantial factor in the mechanisms of neuroplasticity, often disrupted in a plethora of brain pathologies.