104
ARTHUR
HUGHES
with age at transplantation than is the case with replacing grafts. In the
first experiments of this kind, all animals were fixed at a standard
interval after operation, the age of fixation varying from a day or so
before the hatching stage to a similar interval after this event. It was
suspected that the explanation of this difference between grafts of the
two types might be that with supernumerary limb grafts there was an
actual loss of innervating fibers at about the time when the tail was
resorbed. Such a loss would further reduce the proportion of innervated
grafts that had been transplanted at 6-6.5 days. Accordingly, in each of a
further group of embryos at 6.5 days, a hind limb was grafted near a
forelimb, and these animals were fixed at different times after the operation. It was, indeed, found that in those examples fixed before the atrophy
of the tail the proportion of innervated grafts was higher than in those
fixed after this period, though in most examples where the muscles were
no longer innervated, cutaneous fibers were still present.
Further study was then made on forelimbs transplanted near hind
limbs, for, whereas a hind limb grafted in or near the position of a
forelimb is immobile, forelimbs in place of or near the hind limb show
movement when innervated. Thus under these circumstances, any movement in a supernumerary forelimb shows whether it has received or has
still retained motor fibers. Again, in these animals there was both loss
of movement and of innervation of the supernumerary limbs toward the
end of embryonic life, though there were indications that this decrease
preceded the degeneration of the tail (Fig. 11).
It thus appears that the development of limb innervation, as with
other aspects of ontogeny is epigenetic, with its course marked by
recognizable stages of differentiation. Some further evidence is available
concerning the attainment of separate innervation of antagonist muscles,
and the correlated achievement of central inhibitory mechanisms. This
evidence comes from observations on the effect of strychnine and of
related drugs at various stages of development. Strychnine acts on the
nervous system in various ways. One effect is to cause tetanus by abolishing the normal inhibitory reflexes of antagonistic muscles. Eccles (1957,
1964) considers that these reflexes are due to hyperpolarization at
particular synapses, where the drug acts by inhibiting the function of a
postulated transmitter substance concerned with inhibition.
We should, therefore, expect that in a developing animal the effect of
strychnine would become more drastic when antagonistic reflexes are
first established and that, if so, the time when this neural mechanism is
present would be indicated by an increase in sensitivity. Observations on
ARTHUR
HUGHES
with age at transplantation than is the case with replacing grafts. In the
first experiments of this kind, all animals were fixed at a standard
interval after operation, the age of fixation varying from a day or so
before the hatching stage to a similar interval after this event. It was
suspected that the explanation of this difference between grafts of the
two types might be that with supernumerary limb grafts there was an
actual loss of innervating fibers at about the time when the tail was
resorbed. Such a loss would further reduce the proportion of innervated
grafts that had been transplanted at 6-6.5 days. Accordingly, in each of a
further group of embryos at 6.5 days, a hind limb was grafted near a
forelimb, and these animals were fixed at different times after the operation. It was, indeed, found that in those examples fixed before the atrophy
of the tail the proportion of innervated grafts was higher than in those
fixed after this period, though in most examples where the muscles were
no longer innervated, cutaneous fibers were still present.
Further study was then made on forelimbs transplanted near hind
limbs, for, whereas a hind limb grafted in or near the position of a
forelimb is immobile, forelimbs in place of or near the hind limb show
movement when innervated. Thus under these circumstances, any movement in a supernumerary forelimb shows whether it has received or has
still retained motor fibers. Again, in these animals there was both loss
of movement and of innervation of the supernumerary limbs toward the
end of embryonic life, though there were indications that this decrease
preceded the degeneration of the tail (Fig. 11).
It thus appears that the development of limb innervation, as with
other aspects of ontogeny is epigenetic, with its course marked by
recognizable stages of differentiation. Some further evidence is available
concerning the attainment of separate innervation of antagonist muscles,
and the correlated achievement of central inhibitory mechanisms. This
evidence comes from observations on the effect of strychnine and of
related drugs at various stages of development. Strychnine acts on the
nervous system in various ways. One effect is to cause tetanus by abolishing the normal inhibitory reflexes of antagonistic muscles. Eccles (1957,
1964) considers that these reflexes are due to hyperpolarization at
particular synapses, where the drug acts by inhibiting the function of a
postulated transmitter substance concerned with inhibition.
We should, therefore, expect that in a developing animal the effect of
strychnine would become more drastic when antagonistic reflexes are
first established and that, if so, the time when this neural mechanism is
present would be indicated by an increase in sensitivity. Observations on