Engram formation in psychiatric disorders

Peter J. Gebicke-Haerter

Environmental factors substantially influence beginning and progression of mental illness, reinforcing or reducing the consequences of genetic vulnerability. Often initiated by early traumatic events, "engrams" or memories are formed that may give rise to a slow and subtle progression of psychiatric disorders. The large delay between beginning and time of onset (diagnosis) may be explained by efficient compensatory mechanisms observed in brain metabolism that use optional pathways in highly redundant molecular interactions. To this end, research has to deal with mechanisms of learning and long-term memory formation, which involves (a) epigenetic changes, (b) altered neuronal activities, and (c) changes in neuron-glia communication. On the epigenetic level, apparently DNA-methylations are more stable than histone modifications, although both closely interact. Neuronal activities basically deliver digital information, which clearly can serve as basis for memory formation (LTP). However, research in this respect has long time neglected the importance of glia. They are more actively involved in the control of neuronal activities than thought before. They can both reinforce and inhibit neuronal activities by transducing neuronal information from frequency-encoded to amplitude and frequency-modulated calcium wave patterns spreading in the glial syncytium by use of gap junctions. In this way, they serve integrative functions. In conclusion, we are dealing with two concepts of encoding information that mutually control each other and synergize: a digital (neuronal) and a wave-like (glial) computing, forming neuron-glia functional units with inbuilt feedback loops to maintain balance of excitation and inhibition. To better understand mental illness, we have to gain more insight into the dynamics of adverse environmental impact on those cellular and molecular systems. This report summarizes existing knowledge and draws some outline about further research in molecular psychiatry.