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This ‘Past to Future’ Review as part of the 60th anniversary year of the Journal of Neurochemistry focuses on synaptic transmission and associated signalling, and seeks to identify seminal progress in neurochemistry over the last 10 years which has advanced our understanding of neuronal communication in brain. The approach adopted analyses neurotransmitters on a case by case basis (i.e. amino acids, monoamines, acetylcholine, neuropeptides, ATP/purines and gasotransmitters) to highlight novel findings that have changed the way we view each type of transmitter, to explore commonalities and interactions, and to note how new insights have changed the way we view the biology of degenerative, psychiatric and behavioural conditions. Across all transmitter systems there was remarkable growth in the identification of targets likely to provide therapeutic benefit and which undoubtedly was driven by the elucidation of circuit function and new vistas of synaptic signalling. There has been an increasing trend to relate signalling to disease, notably for Alzheimer's and Parkinson's disease and related conditions, and which has occurred for each transmitter family. Forebrain circuitry and tonic excitatory control have been the centre of great attention yielding novel findings that will impact upon cognitive, emotional and addictive behaviours. Other impressive insights focus on gasotransmitters integrating activity as volume transmitters. Exciting developments in how serotonin, cholinergic, L-glutamate, galanin and adenosine receptors and their associated signalling can be beneficially targeted should underpin the development of new therapies. Clearly integrated, multifaceted neurochemistry has changed the way we view synaptic signalling and its relevance to pathobiology.Highlighted are important advances in synaptic signalling over the last decade in the Journal of Neurochemistry. Across all transmitter systems elucidation of circuit function, and notably molecular insights, have underpinned remarkable growth in the identification of targets likely to provide therapeutic benefit in neuropathologies. Another commonality was wide interest in forebrain circuitry and its tonic excitatory control. Increasingly observations relate to signalling in disease and behavioural conditions.