Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was hypothesized to mainly rely on the flexibility of glutamatergic excitatory synapses, whereas inhibitory synapses were assumed relatively invariant, to ensure stable and reliable control of the neuronal network. As a consequence, while considerable efforts were made to clarify the main mechanisms underlying plasticity at excitatory synapses, the study of the cellular/molecular mechanisms of inhibitory plasticity has received much less attention. Nevertheless, an increasing body of evidence has revealed that inhibitory synapses undergo several types of plasticity at both pre- and postsynaptic levels. Given the crucial role of inhibitory interneurons in shaping network activities, such as generation of oscillations, selection of cell assemblies and signal integration, modifications of the inhibitory synaptic strength represents an extraordinary source of versatility for the fine control of brain states. This versatility also results from the rich diversity of GABAergic neurons in several brain areas, the specific role played by each inhibitory neuron subtype within a given circuit, and the heterogeneity of the properties and modulation of GABAergic synapses formed by specific interneuron classes. The molecular mechanisms underlying the potentiation or depression of inhibitory synapses are now beginning to be unraveled. At the presynaptic level, retrograde synaptic signaling was demonstrated to modulate GABA release, whereas postsynaptic forms of plasticity involve changes in the number/gating properties of GABAA receptors and/or shifts of chloride gradients. In addition, recent research indicates that GABAergic tonic inhibition can also be plastic, adding a further level of complexity to the control of the excitatory/inhibitory balance in the brain. The present Topic will focus on plasticity of GABAergic synapses, with special emphasis on the molecular mechanisms of plasticity induction and/or expression.

Recent scientific advances have provided substantial information on the brain circuits and pathways relevant to various aspects of dependence. Neurobiology of Alcohol Dependence highlights the most recent data at the molecular, cellular, neurocircuitry, and behavioral levels, fostering an understanding how neuroplasticity and neuroadaptation occur, and how different neural pathways and neurocircuits contribute to dependence. - Highlights recent advances in understanding alcohol addiction from molecular, cellular, neurocircuitry, and behavioral levels - Integrates several emerging areas of research and discusses the application of novel research techniques to the understanding of alcohol dependence - Chapters authored by leaders in the field around the globe — the broadest, most expert coverage available

Drug addiction is a chronically relapsing mental illness involving severe motivational disturbances and loss of behavioral control leading to personal dev- tation. The disorder af?icts millions of people, often co-occurring with other mental illnesses with enormous social and economic costs to society. Several decades of research have established that drugs of abuse hijack the brain’s natural reward substrates, and that chronic drug use causes aberrant alterations in these rewa- processing systems. Such aberrations may be demonstrated at the cellular, neu- transmitter, and regional levels of information processing using either animal models or neuroimaging in humans following chronic drug exposure. Behaviorally, these neural aberrations manifest as exaggerated, altered or dysfunctional expr- sion of learned behavioral responses related to the pursuit of drug rewards, or to environmental factors that precipitate craving and relapse during periods of drug withdrawal. Current research efforts are aimed at understanding the associative and causal relationships between these neurobiological and behavioral events, such that treatment options will ultimately employ therapeutic amelioration of neural de?cits and restoration of normal brain processing to promote efforts to abstain from further drug use. The Behavioral Neuroscience of Drug Addiction, part of the Springer series on Current Topics in Behavioral Neurosciences, contains scholarly reviews by noted experts on multiple topics from both basic and clinical neuroscience ?elds.

Addiction is a chronic relapsing disorder, which comprises impulsive and compulsive elements. Chronic drug consumption leads to long-term neuroadaptive changes in the brain thus result in an addictive state. However, development of addiction is a complex interaction between genetic, epigenetic and environmental factors. The resulting cellular and molecular changes mediate the transition from controlled drug use to the loss of control over drug-taking and drug-seeking. The human association studies helped us to identify some important genetic factors responsible for the susceptibility to addiction. However, social, environmental circumstances highly influence the development of addiction. Using animal models helps us to examine the underlying neuronal/molecular processes under standardised conditions. The aim of this Research Topic is to summarize our knowledge about the neuroplastic changes, which contribute to the maintenance of drug taking. Data presented in this Research Topic should also provide evidences how acute and long-term neuronal changes during withdrawal result in relapse. How different neuromodulators like endocannabinoids and endogenous opioids contribute to molecular mechanisms that mediate the transition from the controlled, occasional drug consumption to the uncontrolled, escalating drug use and seeking.

GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABAA and GABAB receptors. Recently, a novel form of GABAA receptor-mediated inhibition, termed “tonic” inhibition, has been described. Whereas synaptic GABAA receptors underlie classical “phasic” GABAA receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABAA receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABAA receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This book highlights ongoing work examining the properties of recombinant and native extrasynaptic GABAA receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABAA receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.