BEHAVIORALBIOLOGY 17,555-560 (1976), Abstract No. 5337
BRIEF R E P O R T Genes Influencing Maturation of Nervous System F u n c t i o n
JOSEPH P. HEGMANN 1 and ASTRID B. BOENING
Department of Zoology, University of Iowa, Iowa Oty, Iowa 52242
Lines of mice selected for high and low caudal nerve conduction velocity at 45 days of age remain divergent at 70 and 120 days although conduction velocity by all animals increases substantially during this time. Lines selected for high velocity show largest increases from 45 to 70 days while those selected for low velocity increase more from 70 to 120 days. Thus, genetic correlations between function at different ages are apparently due, in part, to genetic variance for maturation of conduction velocity. Patterns of body weight change do not differ between lines so genetic variance for change in nervous system function seems to be independent of gene influence on morphological development.
At maturity, mice of the DBA/IJ inbred strain display higher caudal nerve conduction velocities than C3H/HeJ mice (White and Hegmann, 1974). In addition, reflex speeds (see Robb and Hegmann, 1974) by animals from these and three other inbred strains differ in the directions expected from differences in caudal nerve conduction velocity if those differences between strains were general for peripheral nerves. During maturation conduction velocity in caudal nerves of both C3H/HeJ and DBA/1J mice increases to the age of 120 days with strong linear and quadratic trends. However, the linear trends are significantly different for the two strains indicating genetic variance for pattern of change in function with age (White and Hegmann, 1974). At a specific chronological age during development (45 days) genetic variance influencing conduction velocity is sufficient to provide substantial response to bidirectional-within-family selection, i.e., to allow the establishment of lines of mice with high and low caudal nerve conduction velocities (Hegmann, 1975). Since nervous system function is so closely related to behavior, gene and environmental differences which influence nervous system function and which modify the pattern of change in that function with age are likely to be important sources of individual differences in behavior. We examined change in conduction velocity with age in lines of mice selected for high and low 1Supported in part by NINDS Grant NS70099. 555
556
HEGMANN AND BOENING
conduction velocity at 45 days of age. The total increase in conduction velocity from the age of 45 to 120 days by nerves from animals in these lines does not differ but the pattern of maturation over that age range seems to be altered between lines. This suggests that genes influencing behavioral differences before physiological maturity may do so by altering maturation of physiological functions relevant to those behaviors. We measured caudal nerve conduction velocity at 45, 70, and 120 days of age for each of 202 mice. The animals were those remaining in the high conduction velocity (H1 and H2), control (C1), and low conduction velocity (L1 and L2) selected lines of mice described by Hegmann (1975) after parents of the next generation had been chosen. Animals representing the first replicate (H1, C1, and L1) were reared contemporaneously with those of the second replicate (H2 and L2); but first replicate subjects were the products of 15 generations of bidirectional-within-family selection for caudal nerve conduction velocity while second replicate animals were from the seventh generation of selection (see Hegmann, 1975). Subjects were reared in stainless steel cages at 24+ I°C and 16hr light, 8 hr dark with food and water available ad lib. Caudal nerve conduction velocities were measured (with subjects anesthetized by 0.06 mg sodium pentobarbitol/g body wt) using three pairs of stainless steel electrodes fixed in a Plexiglas plate to penetrate their tails with known distances between electrode pairs. Compound action potentials were produced using a supramaximal stimulus pulse orthodromic to motor nerves (0.025 msec duration) delivered through the electrode pair nearest the base of the tail and were recorded at the other two electrode pairs using the dual traces of a storage oscilloscope. The distance between pairs of recording electrodes (15 mm) and the time elapsed between peaks of compound action potentials at these sites were used to calculate conduction velocities. Details of these recording procedures including effects of anesthetic and examples of records are presented in Hegmann, 1972. Conduction velocity (in meters per second) and body weight (in grams) were determined for each animal at each of the three test ages. We used the differences between measures at 70 days and at 45 days for each individual to assess early developmental change and the differences between 120-day and 70-day scores to assess late maturation. Average conduction velocities at each of the test ages are presented in Table 1 for females and males of each line. In spite of the fact that the 10 male and 10 female mice with highest conduction velocities from the HI and H2 lines and of lowest conduction velocity in the L1 and L2 lines were used to carry on the selection experiment (that is, were excluded from this study), mean 45-day speeds reflect the pattern of differences expected from response to selection. H1 and L1 mice (both sexes) display the highest and lowest mean speeds and have been subjected to the greatest bidirectional selection intensity (see Hegmann, 1975). Mice from H2 and L2 differ in the expected
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BRIEF R E P O R T Genes Influencing Maturation of Nervous System F u n c t i o n
JOSEPH P. HEGMANN 1 and ASTRID B. BOENING
Department of Zoology, University of Iowa, Iowa Oty, Iowa 52242
Lines of mice selected for high and low caudal nerve conduction velocity at 45 days of age remain divergent at 70 and 120 days although conduction velocity by all animals increases substantially during this time. Lines selected for high velocity show largest increases from 45 to 70 days while those selected for low velocity increase more from 70 to 120 days. Thus, genetic correlations between function at different ages are apparently due, in part, to genetic variance for maturation of conduction velocity. Patterns of body weight change do not differ between lines so genetic variance for change in nervous system function seems to be independent of gene influence on morphological development.
At maturity, mice of the DBA/IJ inbred strain display higher caudal nerve conduction velocities than C3H/HeJ mice (White and Hegmann, 1974). In addition, reflex speeds (see Robb and Hegmann, 1974) by animals from these and three other inbred strains differ in the directions expected from differences in caudal nerve conduction velocity if those differences between strains were general for peripheral nerves. During maturation conduction velocity in caudal nerves of both C3H/HeJ and DBA/1J mice increases to the age of 120 days with strong linear and quadratic trends. However, the linear trends are significantly different for the two strains indicating genetic variance for pattern of change in function with age (White and Hegmann, 1974). At a specific chronological age during development (45 days) genetic variance influencing conduction velocity is sufficient to provide substantial response to bidirectional-within-family selection, i.e., to allow the establishment of lines of mice with high and low caudal nerve conduction velocities (Hegmann, 1975). Since nervous system function is so closely related to behavior, gene and environmental differences which influence nervous system function and which modify the pattern of change in that function with age are likely to be important sources of individual differences in behavior. We examined change in conduction velocity with age in lines of mice selected for high and low 1Supported in part by NINDS Grant NS70099. 555
556
HEGMANN AND BOENING
conduction velocity at 45 days of age. The total increase in conduction velocity from the age of 45 to 120 days by nerves from animals in these lines does not differ but the pattern of maturation over that age range seems to be altered between lines. This suggests that genes influencing behavioral differences before physiological maturity may do so by altering maturation of physiological functions relevant to those behaviors. We measured caudal nerve conduction velocity at 45, 70, and 120 days of age for each of 202 mice. The animals were those remaining in the high conduction velocity (H1 and H2), control (C1), and low conduction velocity (L1 and L2) selected lines of mice described by Hegmann (1975) after parents of the next generation had been chosen. Animals representing the first replicate (H1, C1, and L1) were reared contemporaneously with those of the second replicate (H2 and L2); but first replicate subjects were the products of 15 generations of bidirectional-within-family selection for caudal nerve conduction velocity while second replicate animals were from the seventh generation of selection (see Hegmann, 1975). Subjects were reared in stainless steel cages at 24+ I°C and 16hr light, 8 hr dark with food and water available ad lib. Caudal nerve conduction velocities were measured (with subjects anesthetized by 0.06 mg sodium pentobarbitol/g body wt) using three pairs of stainless steel electrodes fixed in a Plexiglas plate to penetrate their tails with known distances between electrode pairs. Compound action potentials were produced using a supramaximal stimulus pulse orthodromic to motor nerves (0.025 msec duration) delivered through the electrode pair nearest the base of the tail and were recorded at the other two electrode pairs using the dual traces of a storage oscilloscope. The distance between pairs of recording electrodes (15 mm) and the time elapsed between peaks of compound action potentials at these sites were used to calculate conduction velocities. Details of these recording procedures including effects of anesthetic and examples of records are presented in Hegmann, 1972. Conduction velocity (in meters per second) and body weight (in grams) were determined for each animal at each of the three test ages. We used the differences between measures at 70 days and at 45 days for each individual to assess early developmental change and the differences between 120-day and 70-day scores to assess late maturation. Average conduction velocities at each of the test ages are presented in Table 1 for females and males of each line. In spite of the fact that the 10 male and 10 female mice with highest conduction velocities from the HI and H2 lines and of lowest conduction velocity in the L1 and L2 lines were used to carry on the selection experiment (that is, were excluded from this study), mean 45-day speeds reflect the pattern of differences expected from response to selection. H1 and L1 mice (both sexes) display the highest and lowest mean speeds and have been subjected to the greatest bidirectional selection intensity (see Hegmann, 1975). Mice from H2 and L2 differ in the expected
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