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J. S. GRIFFITH
There is definite evidence for local protein syntheses in various axons
[18, 37] and, at least in one case, this appears to be outside the mitochondria
[38]. Although electron microscopic techniques have failed to show ribosomes in axons [17, 18], there does seem to be ribosomal RNA [43] and perhaps also DNA [19] which may be directing this local synthesis.
e) Compounds Which Interfere with Protein or RNA Synthesis
If the laying down of new long-term memory involves, as an essential
part, the synthesis of new protein or new mRNA, then it must be inhibited
by any compound which prevents that synthesis. For this reason, several
investigators have injected puromycin and other compounds into the brains
of various animals, before and after learning, to determine the effect on
memory. The results favour the view that the early phases of memory
storage do not involve such new synthesis [1, 3].
However, the effects on the later phases of storage were soon found to
be less simple. Puromycin and acetoxycycloheximide (AC) both inhibit
protein synthesis, although by different mechanisms [20]. In the goldfish,
they both appear to prevent long-term memory [1], but in the mouse only
puromycin does, but not AC or cycloheximide [4,21,24] (actinomycin D
was found to have no effect on memory in the mouse [5, 12]). Furthermore,
AC injected together with puromycin can actually protect against the influence of the latter upon memory [21].
It is becoming apparent now that the situation is even more complicated
than this. The effect of puromycin seems to be dependent also upon environmental factors [14] and even upon the subsequent injection of saline [22],
whilst AC does seem to have a transient effect in mice after all [23]. Also it
has been suggested that puromycin may work by producing an increased
susceptibility of the animal to seizures [13] and that some of its effects may
be caused by the brain lesion arising from the puncture by the injecting
needle [6]. Evidently no clear-cut picture emerges at the present time, and
it is to be hoped that workers using this sort of approach will not be discouraged from continuing what is surely, even now, a very hopeful experimental procedure.
f) The Nerve Growth Factor
The nerve growth factor (NGF) is a protein which stimulates growth
of embryonic sensory and sympathetic, and mature sympathetic, nerve
cells [40]. Its properties are interesting in connection with memory because
of the possibility that the latter is based upon growth stimulated by similar
proteins [29]. Its effects are inhibited by actinomycin D [41], which suggests
that it is operating at the level of transcription and may be acting as an
inducer. In view of the discussion in section d, it would be of great interest
to know its exact site of action in the cell.
J. S. GRIFFITH
There is definite evidence for local protein syntheses in various axons
[18, 37] and, at least in one case, this appears to be outside the mitochondria
[38]. Although electron microscopic techniques have failed to show ribosomes in axons [17, 18], there does seem to be ribosomal RNA [43] and perhaps also DNA [19] which may be directing this local synthesis.
e) Compounds Which Interfere with Protein or RNA Synthesis
If the laying down of new long-term memory involves, as an essential
part, the synthesis of new protein or new mRNA, then it must be inhibited
by any compound which prevents that synthesis. For this reason, several
investigators have injected puromycin and other compounds into the brains
of various animals, before and after learning, to determine the effect on
memory. The results favour the view that the early phases of memory
storage do not involve such new synthesis [1, 3].
However, the effects on the later phases of storage were soon found to
be less simple. Puromycin and acetoxycycloheximide (AC) both inhibit
protein synthesis, although by different mechanisms [20]. In the goldfish,
they both appear to prevent long-term memory [1], but in the mouse only
puromycin does, but not AC or cycloheximide [4,21,24] (actinomycin D
was found to have no effect on memory in the mouse [5, 12]). Furthermore,
AC injected together with puromycin can actually protect against the influence of the latter upon memory [21].
It is becoming apparent now that the situation is even more complicated
than this. The effect of puromycin seems to be dependent also upon environmental factors [14] and even upon the subsequent injection of saline [22],
whilst AC does seem to have a transient effect in mice after all [23]. Also it
has been suggested that puromycin may work by producing an increased
susceptibility of the animal to seizures [13] and that some of its effects may
be caused by the brain lesion arising from the puncture by the injecting
needle [6]. Evidently no clear-cut picture emerges at the present time, and
it is to be hoped that workers using this sort of approach will not be discouraged from continuing what is surely, even now, a very hopeful experimental procedure.
f) The Nerve Growth Factor
The nerve growth factor (NGF) is a protein which stimulates growth
of embryonic sensory and sympathetic, and mature sympathetic, nerve
cells [40]. Its properties are interesting in connection with memory because
of the possibility that the latter is based upon growth stimulated by similar
proteins [29]. Its effects are inhibited by actinomycin D [41], which suggests
that it is operating at the level of transcription and may be acting as an
inducer. In view of the discussion in section d, it would be of great interest
to know its exact site of action in the cell.