Ontogeny of behavioral sensitivity to strychnine in the chick embryo: evidence for the early onset of CNS inhibition.

The development of behavioral sensitivity to strychnine has been studied in the chick embryo between day 7 of incubation and 1 day posthatching. The earliest response to systemically applied strychnine was a marked depression of spontaneous motility at high concentrations of the drug. Lower concentrations had no effect at this time (6-7 days). About 2 days later, on day 81/2 or 9, strychnine induced a statistically reliable increase in spontaneous motility (hyperactivity). This consisted of a brief (i.e. 1-2 min) excitatory response which was followed by a return to baseline activity levels in the case of low drug concentrations, or a depression of activity in the case of low drug concentrations, or a depression of activity in the case of higher concentrations. By 11 days of incubation the brief excitatory response following strychnine had increased in duration to about 4 min. This was also the case for 13-day embryos. At no time between 7 and 13 days were convulsions produced by strychnine, even at concentrations several times greater than that required to induce hyperactivity. For the first time at 16 days myoclonic convulsions were observed following strychnine. These usually began soon after the initial hyperactivity and frequently lasted for as long as 30 min. At the same time the sensitivity of the embryo to strychnine increased, compared to earlier stages. By 18 days strychnine most often induced an immediate convulsive response without the preceding brief hyperactivity. This was also typical of newly hatched chicks. The systemic application of glycine at 9 and 13 days of incubation produced a slight, but statistically reliable, depression of ongoing spontaneous motility, consistent with what one might expect if glycine were acting as an inhibitory neurotransmitter. It typically took between 3 and 4 min following injection for this glycine response to occur. Biochemical, electrophysiological and neuroanatomical evidence was reviewed in an attempt to support the suggestion that the strychnine and glycine data summarized above may reflect the presence of strychnine-sensitive postsynaptic inhibitory processes in the chick spinal cord. Additionally, comparative data on the relative onset of excitatory and inhibitory processes in the developing spinal cord were discussed. It was concluded that, although the data are still imcomplete concerning the question of whether, developmentally, inhibition is a primary or secondary acquisition, inhibitory mechanisms nevertheless appear rather early during vertebrate neurogenesis.