NEUROPHYSIOLOGICAL, PHARMACOLOGICAL AND MORPHOLOGICAL PROPERTIES OF HUMAN CAUDATE NEURONS RECORDED IN-VITRO

Tissue samples from the caudate nucleus were obtained from eight child ren (eight to 172 months of age) who underwent hemispherectomies for t he relief of intractable seizures. Neurophysiological, pharmacological and morphological properties of caudate neurons were characterized by intracellular recordings in an in vitro slice preparation. These prop erties were compared with those of tissue obtained from animal studies . Electrophysiological properties of human caudate neurons that were s imilar to those of cat caudate and rat neostriatal cells included rest ing membrane potential, input resistance, action potential rise time, fall time, duration and action potential afterhyperpolarization amplit ude, as well as the general characteristics of locally evoked synaptic responses. Properties that were different included action potential a mplitudes and time-constants. Human caudate neurons also displayed res ponses similar to those of cat caudate or rat neostriatal cells to man ipulation of excitatory amino acid receptor systems and to dopamine ap plication. Kynurenic acid, a broad-spectrum excitatory amino acid rece ptor antagonist, decreased the amplitude of evoked synaptic responses, indicating that they were partially mediated by excitatory amino acid s. In Mg2+ free Ringer's solution, the amplitudes and durations of pos tsynaptic responses were increased and bursts of action potentials wer e induced. These effects were mediated by activation of N-methyl-D-asp artate receptors since they were blocked by 2-amino-5-phosphonovalerat e, a specific N-methyl-D-aspartate-receptor antagonist. Iontophoretic application of N-methyl-D-aspartate also induced membrane oscillations and bursts in almost all caudate neurons. Dopamine decreased the ampl itude of postsynaptic responses, an effect antagonized by domperidone, a selective D, dopamine receptor antagonist. Developmentally, the gre atest change was an increase in action potential amplitude, although i nput resistance decreased and action potential afterhyperpolarization amplitude increased. Postsynaptic responses were similar across age. A ll but one of the caudate neurons identified by intracellular injectio n of biocytin or Lucifer Yellow were medium-sized spiny cells. These e xperiments show that human caudate neurons display a number of electro physiological properties similar to rat neostriatal or cat caudate neu rons recorded in brain slices. Furthermore, few electrophysiological p arameters changed significantly over the age period examined suggestin g that the human caudate at eight months displays many of the neuronal functions of the more mature caudate nucleus.