Neural Activity and the Development of Brain Circuits

The behaviour of an animal depends fundamentally on how the neurons in its nervous system are connected with one another and the motor output. During early human development over 100 billion neurons each establish from dozens to thousands of connections with one another and with muscle fibres. At all levels of the nervous system, precise connections emerge from initially imprecise patterns of contact. How is this enormously complex brain circuitry organized with any degree of fidelity during development? Among brain systems, the question has been addressed most extensively in the developing visual pathway. Data show that the final precision of brain circuitry in the visual system relies heavily on neural activity, while the initial targeting of axons to the appropriate regions of the nervous system occurs independently of it. This activity is generated by the transduction of stimuli in the environment, but it can also occur spontaneously in early development before the sensory mechanisms are fully functional. Appropriate patterns of neural activity can lead to themodification of synaptic ‘strengths’. Changes in synaptic strength, then, may provide a signal for identifying functionally useful circuits. Particular molecules that act downstream of electrical activity to shape brain circuitry and modify synaptic strength have been identified. These include the N-methyl-d-aspartate (NMDA) receptor, nitric oxide and a class of molecules called neurotrophins. The sensitivity of brain circuitry to the absence of patterned neural activity is limited to ‘critical periods’ during early development. Interestingly, the degree of plasticity of synaptic strength is highest during these times. The critical periods themselves exhibit some plasticity; they can be shifted by altering the rearing environment or by increased neurotrophin production. Visual system