Examining neocortical circuits: some background and facts

The first definitive studies of where afferents to cerebral cortex terminate were made possible by the finding that as they degenerate axon terminals become electron dense. Gold toning of Golgi impregnated neurons allowed the postsynaptic targets of these afferents to be identified by electron microscopy and also allowed the termination sites of axons from a variety of types of cortical neurons to be ascertained, while the development of antibodies to GAD and to GABA made it possible to determine which types of cortical neurons are inhibitory. Subsequently the use of gold toned, Golgi impregnated material to examine neuronal connectivity was made redundant by the development of techniques that allowed the physiological properties of cortical neurons to be evaluated in neurons filled intracellularly with markers. Intracellular filling showed the axonal trees of cortical neurons are much more widespread than had been revealed by Golgi impregnations. As a result of numerous studies of the axons of identified neurons, we know a great deal about where most of the different types of neurons in cerebral cortex form their synapses, but on the other side of the picture there is a dearth of information about the origins of the inputs that specific types of cortical neurons receive. However, it is evident that each cortical neuron is the focus of input from many other neurons, and on the basis of the available data it is estimated that a single pyramidal cell in cortex receives its input from as many as 1,000 other excitatory neurons and as many as 75 inhibitory neurons.