Postnatal development of electrical activity in the hamster spinal cord studied in an in vitro preparation

Abdul Razzak, Rima (1992) Postnatal development of electrical activity in the hamster spinal cord studied in an in vitro preparation. University of Southampton, Doctoral Thesis.

Abstract

The dorsal root reflex (DRR) is a volley of antidromic action potentials that can be recorded emerging from dorsal roots on stimulation of an adjacent dorsal root. In addition to the evoked DRR, the hamster isolated spinal cord maintained in Mg-freeACSF at 25-27^o C exhibits characteristic bursts of spontaneous action potentials emerging from the cord along the dorsal roots or in the dorsal horn. It was shown that in barbiturate anaesthetized cats, the DRR does not appear before day 4 postnatal and increases to a maximum within the fourth week of life, before declining to lower adult values (Bawa, 1988). The aim of this project is to study the developmental changes in the frequency and pattern of spontaneous activity, and in the pharmacological sensitivity during the first 7 weeks of life. The study revealed that the pattern of spontaneous firing in animals younger than two weeks, was principally single action potentials, giving a single mode on Inter-Spike Interval plots. Above the age of three weeks, dorsal root/horn spontaneous activity was dominated by bursts of action potentials shown as bimodal ISI plots. Cross correlation studies on dorsal horn spontaneous activity between two sites of recording showed that the indices of cross correlation increase with age, suggesting that intersegmental links mature postnatally in the cord. Lumbar and sacral dorsal roots were stimulated at twice threshold, and the evoked responses in the dorsal horn were used to construct Peri-Stimulus Time Histograms. Responses were evoked at all ages, and appeared as a peak on the PSTH. In animals older than 3 weeks, this was followed by a depression of spontaneous activity between 200 and 400 ms after stimulation, whereas in younger animals, the number of action potentials recorded during this period was increased above the spontaneous level. This indicates that excitatory processes responsible for generation of the DRR are active within 1 week of birth, whereas inhibitory events develop later in life. The pharmacological studies show that the adult pattern of spontaneous activity in dorsal roots and dorsal horn are insensitive to addition of 1 mM Mg²⁺ or 5μM D-AP5. Incords from young animals, this activity was depressed by both Mg^2+and AP5, indicating an involvement of NMDA receptors in the generation of spontaneous activity in the young, but not in the mature animals. Studies of the effects of addition of NMDA for 10 mins on the frequency of spontaneous activity revealed that in 5-6 week old animals, the frequency was depressed to 66.4% of the control value. In the second week of life, NMDA produced a complex sequence of changes in the firing frequency. The predominant pattern was a short latency excitation (1-5 mins) followed by a decrease in the firing rate which persisted for the remainder of the 10 minute period. These results suggest that NMDA receptors may be more numerous or more functional in young animals.

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