[Neuroscience at the end of the 2nd millennium: a shift in paradigms]

The new neuroscience data rapidly accumulating by the end of the second millennium calls for radical revision of many long-established and widely accepted postulates. This paper reviews some data leading to new concepts of life and work of neurons. The adult brain contains stem cells which are the source of the precursors for all main types of the brain cells: neurons, astrocytes, and oligodendroglia. These cells can substitute the deteriorating elements in the adult and even old brain. The neurons occur to be highly resistant to lesion of their processes as well to anoxia, and inhibitory neurons are shown to be especially stable in some pathological conditions. Changes in the afferent inputs result in various types of rapid compensatory morphological and functional reorganizations at different levels. Thus, the previous fatalistic view of the nervous system is substituted now for an optimistic one regarding various possibilities of prolongation and restoration of normal functioning of the brain. Simultaneously, our concepts of the neurons changed drastically. An unitary neuron may operate by several neurotransmitting substances; their synaptic influences upon the dendrites may evoke the active propagation of calcium and sodium spikes, their axons may differentially release transmitter substances depending on parameters of excitation. All neuronal functions are helped and controlled by astroglia, which participates in the synthesis of transmitters and protects the neurons from the excitotoxic death. Besides the synaptic interactions between the neurons, there exist other types of communications, such as volume conduction of transmitters after their spillover from the excited synapses and non-synaptic (varicose) zones, as well as exchange of molecules and ions through the gap junctions. A complex picture of interneuronal communications with multiple synaptic, presynaptic, and parasynaptic interactions is further complicated by the intimate participation of neurotrophic substances and "mediators of the immune system"--cytokines in these processes. The mutual regulatory influences between neurotransmitters, neurotrophic, and neuroimmune systems show that in normal conditions all they are working in concert. This increase in number of factors determining the final result of interaction between the neurons contributes new difficulties to the development of theoretical concepts or simulation of brain functions. In this context it is possible to speak about a certain crisis of theoretical neurobiology at present, because multiplicity of fine details obtained by molecular neurobiology and neurogenetics cannot be integrated in a coherent view of the brain functions. Overcoming the present gap between the analytic and synthetic approaches to understanding the brain work will be the main aim for the neurobiologists of the third millennium.