Application of in vivo patch-clamp technique to pharmacological analysis of synaptic transmission in the CNS

Slice preparations as well as acutely dissociated and cultured neurons from various regions in the CNS have been widely used to analyze pharmacological properties of synaptic responses and receptors expressed at the pre- and post-synaptic sites. However, the essential properties are not obviously different from neuron to neuron. These characteristics of neurons in the CNS make it difficult to elucidate their functional significances. It is, therefore, preferable that the pharmacological analysis should be made from identified neurons by stimulation of identified inputs. The in vivo patch-clamp recording technique allows us to clarify the synaptic responses evoked by the various known natural stimuli applied to the skin or other parts and makes it possible to interpret with more certainty the behavioral changes by synaptic plasticity observed at the single cell level. Although the in vivo technique has obvious advantages in analysis of physiological responses, this method is, however, confined so far to neurons located at the near surface of the CNS for pharmacological analysis, because of the diffusion problem of the chemical to deeper neurons. Thus, combinatorial studies with dissociated or cultured neurons or with slice preparations are clearly required for further understanding of pharmacological properties of neurons in the CNS.