Effects of early hypo- and hyperthyroidism on development of rat cerebellar cortex. IV. The parallel fibers

Abstract Parallel fiber growth was studied during the postnatal period and adulthood in controls and rats made hypo- or hyperthyroid from birth, using a lesioning and degeneration staining method for the direct determination of parallel fiber length. In control animals, parallel fiber growth was rapid from 10 to 30 days of age, followed by a period of much slower growth into adulthood, when parallel fibers reached a maximum length of approximately 5 mm. Hypothyroidism retarded parallel fiber development, especially at 15 and 30 days, resulting in permanently shorter parallel fibers in at least one lobule (IV). Hyperthyroidism accelerated and prolonged growth of parallel fibers, producing adult fibers as much as 1.5 mm longer than controls (lobule V). The possible functional significance of this effect is discussed. The consequences of neonatal hypo- and hyperthyroidism for the synaptic capacity of adult parallel fibers was also examined using the rapid Golgi method. Parallel fibers of hypothyroid animals were dificient in the density of varicosities (sites of synapses with Purkinje cells) along their surface. In combination with the reduced length of these axons, this resulted in a deficit in the total number of synaptic sites per parallel fiber, a result consistent with our previous finding of a general synaptic hypoplasia in the hypothyroid molecular layer. Hyperthyroidism, while stimulating increased parallel fiber growth, did not change the density of varicosities along the parallel fibers. The increased length of these axons, however, did produce an increase in the total number of synaptic sites per parallel fiber. This finding substantiates our previous prediction that, due to the pronounced deficit in granule cells, each parallel fiber must make more than the normal number of synapses in order to achieve the normal synaptic density observed in the adult hyperthyroid molecular layer. This raises the possibility that hyperthyroidism may change the rate of synaptogenesis mainly as a consequence of the stimulation of axonal (and dendritic) growth rather than by affecting synaptogenic events directly. Implications for hormonal control of rates of axonal growth and synaptogenesis in the developing cerebellum are considered, as well as possible mechanisms responsible for these effects.