Download A Brain Adaptation View of Plasticity: Is Synaptic Plasticity An Overly

A Brain Adaptation View of Plasticity: Is Synaptic Plasticity An Overly
Limited Concept?
There is a long tradition, traceable to the early musings
of Ramon y Cajal, of focusing upon the neuron as the only
plastic cell type of any importance within the brain, and
upon the synapse as the only important plastic aspect
regulating the interactions among neurons. While neuronal
plasticity is without question an important aspect of brain
function, it has become increasingly clear that other
cellular elements of brain are plastic and that their
plasticity can contribute to brain function. Moreover, it
is becoming clear in work of others that there are multiple
forms of synaptic plasticity: the synaptic number response
to a complex environment, for example, occurs in animals
genetically rendered incapable of the most common form of
LTP. Our work and that of others indicates that
oligodendrocytes, astrocytes, vasculature, and perhaps
other cellular elements exhibit plasticity quantitatively
equivalent to that of neurons in the developing and mature
brain and that modifications of these cellular elements may
be brought about by experience. It also suggests that
multiple forms of plasticity may occur at the synapse. In
short, while memory researchers largely focus on naturallyand artificially-induced changes in synaptic connectivity,
the brains of real animals (and presumably people) in realworld situations are in a dynamic state in which synaptic
adjustment may in some cases be a relatively small part of
the mix. The intent of this review is to consider the data
that point to this view and consider how we might assess
nonsynaptic effects of learning and/or determine whether
the effects of learning upon measures of brain functional
organization may already be affected by these nonsynaptic
changes.
Since the early speculations of Tanzi and Ramon y
Cajal, the synapse has been the principal proposed site of
plasticity underlying learning and memory in the brain.
Tanzi () initially emphasized the possibility of strength
changes in pre-exiisting connections while Ramon y Cajal ()
stressed the formation and loss of connections. The
ability to examine these possibilities depended on
development of adequate tools, but, by the early 1970s,
electrophysiological and anatomical evidence for the
ability of the nervous system to alter its functional
connectivity in accord with its experience was becoming
reasonably well established. Electrophysiologically, longterm potentiation had been described (Bliss and Lomo,
1973). Anatomically, there was evidence that synapses in
the late developing and adult nervous system could both
form and change in size in response to experience;
innervation of neurons by surviving axons occurred
spontaneously in response to denervation (Sprouting,
Raisman, Lynch references) [when was first comparable
Aplysia report?]; exposure to a complex environment from
weaning through adolescence increased dendritic field
dimensions (Volkmar & Greenough, 1972) and synaptic size
(West & Greenough, 1972) in the rat visual cortex. This
paper summarizes progress in understanding the brain
plasticities thought to be associated with learning and
memory, focusing heavily on our own work, since those
relatively early beginnings.
A relatively early specific demonstration that
synapses formed in response to experience was the report by
Turner and Greenough (1983, 1985) that there were more
synapses per neuron in upper layers of the visual cortex in
rats that had been reared from weaning in a complex
environment. This rearing and adult housing paradigm,
pioneered by Hebb (1949) and his students (e.g. Hymovitch,
19xx) using behavioral measures, and first used as a tool
for exploring brain plasticity by Krech, Rosenzweig and
Bennett (19xx), has been used extensively to examine the
range of plasticity of various elements of brain other than
neurons, but most of these results have failed to become
incorporated into the continuing literature on brain
plasticity. Early in this history, Diamond ** (19xx)
reported that glial cells in visual cortex exhibited
morphological changes in response to experience in paralell
with the changes reported in neuronal dendrites and
synapses.
We have subsequently examined plasticity of nonneuronal elements of the cerebral cortex in response to
complex environment exposure in some detail.
Following up on these initial demonstrations of
dendritic and synaptic responsiveness to rearing
conditions, neuronal responsiveness to has subsequently
been demonstrated in a wide variety of brain structures:
hippocampus (Mosers et al.), basal ganglia (Comery papers),
cerebellar cortex (Greenough, McDonald, Parnisari, , 19xx)—
someone to fill this in with both our data and others.**
At this point, neuronal plasticity seems to be the rule
rather than the exception in CNS structures, although there
are some striking failures to demonstrate it in some cases
(Kleim LCN; is this the right thing to say? Kleim now has
data showing dentate/interpositus?? plasticity in eyeblink
conditioning.
Similarly, these forms of neuronal plasticity occur
relatively consistently across the age spectrum and do not
appear to be restricted to particular critical or sensitive
periods of development. Effects of adult exposure to a
complex environment have been shown to affect dendritic
field dimensions in the visual cortex of adult, middle-aged
and even elderly rats (e.g., Juraska et al., 1980; Green et
al., 1983; elderly reference). Similarly, cerebellar
CHAPTER WORKING NOTES:
Tissue cultures lacking astrocytes—how good a model?
Lack of astro part of ECM. Lack of basis for TPA, other
actions probably involved in synaptogenesis. MMP3, MMP6,
MMP9 (Metalomatrix proteins), stromolysin, gelatinase.
Roles of Astros, ECM, TPA, etc. in synaptogenesis;
adhesions; rec aggregation
Incorporate Harris, Matus, Segal. Motility and shape
issues. Put together a model, slow accumulation of
synapses via overproduction-selection as a basis for the
stable long-term substrate of memory; plus fast shape
changes, PSD size, perfs, interpret multiple synapses from
local and wiring diagram view.
Also local regulation in dendrites; protein synthesis;
dynamic view; incorporate FMRP in this context
Do also a TINS—go head to head with Menahem