Role of non-neuronal changes in learning / activity based plasticity. –
MAINTENANCE!!!!
One is Brenda's 1994? Paper showing the correlation between synapse number
and astrocyte Vv. The other is Jeff's astrocyte persistence paper. Discussed
already?????
Regulation of Astrocyte Plasticity
Is this redundant? This was mentioned in the section on non-neuronal
plasticity and perhaps should merely be elaborated more in that section there are
two studies that might be discussed in more detail either in that section or here.
Tj's ensheathment paper fits in this discussion. The point of putting it here is by
way of a segue into a discussion of the tendency to ignore non neuronal (or even
nonsynaptic) changes.
BILL, IT SEEMS THAT MOST OF THIS PARAGRAPH PROVIDES FURTHER
SUPPORT FOR THE NON-GLOBAL (METABOLIC) EFFECT OF ACTIVITY ON
PLASTICITY, BUT DOESN’T SAY MUCH ABOUT “DIFFERENT TYPES OF
PLASTICITY. MAYBE YOU CAN INTEGRATE IT INTO OTHER PARTS OF
THE TEXT, OR MOVE THE WHOLE THING…..
Although differential experience can induce widespread plastic changes
within the brain, the concept that different kinds of plasticity occur in different
situations, and suggests that the type and location of the plasticity is dependent
upon the nature of the experience (Morris et al., 1989; Klintsova & Greenough,
1999). As discussed above, motor training experiences that involve the
development of motor skill induce changes in synapse number within the
cerebellar and motor cortices while extensive repetition of unskilled movements
causes non-neuronal changes, but no change in synapse number (Black et al.,
1990; Kleim et al., 1996; Kleim et al., 1998c; Kleim et al., 2002b). Similarly, the
acquisition of skilled forelimb movements resulted in reorganization of forelimb
movement representations within motor cortex (Nudo et al., 1996; Kleim et al.,
1998a) while extensive repetition of unskilled movements (Plautz et al., 2000;
Kleim et al., 2002a) and forelimb strength training (Remple, et al., 2001) were
without effect. In contrast, strength training increased synapse number in the
ventral spinal cord but motor skill training was without effect (Kleim, et al., 2001).
Differential patterns of plasticity can also be observed across types of learning
that seemingly use similar neuronal pathways. For example, motor skill training
does not alter synapse number within the deep cerebellar nuclei (Kleim, et al.,
1998) whereas eye blink conditioning does CAN’T END SENTENCE LIKE THIS
(Bruneau, et al., 2001). BUT WHO IS SAYING THAT THESE DIFFERENT
FORMS OF ACTIVITY ARE UTILIZING THE SAME AREAS??? CAN WE BE
MORE SPECIFIC ABOUT “DEEP CEREBELLAR NUCLEUS”?? Even within a
specific learning experience plasticity can be found within some brain regions but
not others. DOESN’T THIS SIMPLY SAY THAT NOT ALL BRAIN AREAS ARE
INVOLVED IN ALL BEHAVIORS? Complex housing causes dendritic
hypertrophy in visual and sensory cortices but not in prefrontal or temporal cortex
(Kolb ref). SAME ISSUE AS ABOVE. Skilled forelimb reach training causes a
reorganization of movement representations and an increase in synapse number
within the caudal IS THIS EQUIVALENT TO PRIMARY MOTOR CORTEX?
forelimb area but not within the neighboring rostral WHEREAS THIS IS
SUPPLEMENTARY MOTOR CORTEX? IF SO, THERE ARE CLEAR REASONS
WHY CHANGES MIGHT BE EXPRESSED IN CAUDAL AND NOT ROSTRAL
AREAS forelimb area (Kleim, et al., 2002). THIS SEEMS OUT OF PLACE,
IMPORTANT, BUT NOT IN THE RIGHT SPOT. Interestingly, reach training
induced increase of field potential in forelimb contralateral to preferred limb (vs.
ipsilateral) in layer II/III (Rioult-Pedotti, et al., 1998), suggesting a selective
strengthening of horizontal cortical connections associated with learning new
motor skills. Complex motor training is associated with an increase in synapse
number within the cerebellar cortex (Kleim, et al., 1998) but not within the deep
cerebellar nuclei (Kleim, et al., 1998). REDUNDANT FROM ABOVE. The
specificity of the plasticity can even be reduced to subpopulations of neurons
within the same brain region. For example, complex housing causes dendritic
hypertrophy within cerebellar Purkinje cells but not granule cells (Floeter and
Greenough, 1979). Reach training causes dendritic hypertrophy within layer II/III
of the motor cortex that is restricted to a specific class of pyramidal cells (Withers
and Greenough, 1989). Finally, plasticity can even be observed to be restricted
to specific afferents onto individual neurons. Complex motor skill training causes
an increase in parallel fiber synapses onto Purkinje cells but not climbing fibers
(Kleim, et al., 1998). Eyeblink conditioning causes an increase in the number of
excitatory synapses within the anterior interpositus without alter inhibitory
synapse numbers (Bruneau, et al., 2001). Similarly strength training causes an
increase in excitatory but not inhibitory axosomatic synapses within the ventral
spinal cord (Kleim, et al., 2001). THIS PREVIOUS SECTION IS JUST KIND OF
PATCHY, USEFUL BUT NOT CONSISTENT WITH SPIRIT OF PAPER.
THESE CONCEPTS SEEMS TO GO WITH THIS SECTION:
Synaptic specificity supported by “synaptic tag” that is localized and
protein-synthesis independent (Frey and Morris, 1997). Fits concept of
metaplasticity in that history of synapse (even sub optimal stimulation patterns)
pre-disposes synapse to subsequent modification.
Could consider integrating notion of differential parameters
necessary/sufficient to induce LTP (emphasize model of learning, not that it is
equivalent or necessary for) in multiple areas of the brain. That one type of
stimulus does not result in the same effect in numerous areas of the brain
suggests (obviously) differential make-up of that area and surely different
mechanisms. This notion would simply parallel our argument of different “types of
plasticity” (as defined anatomically), with physiological correlates (Yun, et al.,
2002); (Trepel and Racine, 1998).
This goes on the end or might be placed elsewhere:
A note on Long-term potentiation
CHANGE ORDER TO REFLECT MORPHOLOGICAL CHANGES
ASSOCIATED WITH LTP (EB, MS) AND SUPPORTED BY AS. Engert and
Bonhoeffer have reported apparent synaptogenesis in vitro in association with
LTP induction. High-frequency stimulation produced enhanced growth of
filopodia-like protrusions in CA1 slices (viewed with 2-photon), an effect that was
blocked by NMDAR antagonism (Maletic-Savatic, et al., 1999).
ALSO WORK OF ANDERSEN AND SOLENG (Andersen and Soleng,
1998) WHO SHOWED SYNAPTOGENESIS ASSOCIATED WITH LTP AND
SPATIAL LEARNING (THEY SUGGESTED BIFURCATION/BRANCHING OF
EXISTING SPINES) END WITH EMPHASIS THAT LTP IS A NEURONAL
MODEL OF LEARNING.
At least 3 studies, HOWEVER, dissociate LTP from spatial behavior and
morphological change. The primary point I want to make is the apparent
dissociation of LTP from EC effects on synapses published by J. Tsien in Nature
Neuroscience. This suggests that LTP and synaptogenesis are independent
phenomena. I am not sure what the range of the evidence is or the weight of it
(e.g., other more recent work that bears on this issue, most of which are likely to
have cited both of the above studies (Tsien and E-B) and hence should be
locatable via the science citation index, which I have not used for the last million
years), but the dissociation to me seems most powerful-synapse addition may
mediate LTP, but synapse addition need not involve an LTP-like process for its
induction.
IS THIS THE VENUE TO EVEN BRING UP FRAGILE X/FMRP????
On the Horizon: A Role for Protein Synthesis at the synapse
Since the first report of morphological evidence for protein synthesis at the
synapse (Steward & Levy, 1992) there has been a growing body of literature
investigating this phenomenon. Some forms of synaptic and dendritic protein
synthesis have been shown to be activated by metabotropic glutamate receptors
(mGluR) in some cases (e.g., Weiler & Greenough, 1993; Weiler et al., 1994,
1997; Eberwine PNAS-still in press?) and by NMDA receptors as well (Sheetz
et al., 2000). Proteins synthesized at synapses include the fragile X protein
FMRP and calcium/calmodulin-dependent protein kinase II (CAMKII). FMRP has
also been shown to be necessary for the mGluR-dependent synthesis, which is
not observed in FMR1 knockout mice (cite Spangler abstract). Plasticityinducing forms of electrical stimulation have been shown to trigger the
transcription and transport of mRNA for the protein ARC to dendritic sites of
stimulation, where it is translated (Steward and Worley references). mGluR1
activation, ARC synthesis and CAMKII activity have been proposed to be
involved in various forms of plasticity (Huber/Bear work; Steward; Mary
Kennedy), although details of the specific functions of synaptic or dendritic
protein synthesis are still under investigation. Do you think we need to say
anything more here? The chapter is really not "about" this, and I am not sure (but
open to suggestions) what additional data makes sense to include.
In summary, brain plasticity appears to be a phenomenon that is not
restricted to elements that are neuron-specific. In fact, it could be argued that
neuronal plasticity is but a small fraction of the overall changes that occur in
response to experience and that we are just beginning to understand the
importance of these other forms of brain plasticity. A big waving of our hands to
and draw grand conclusions, followed by speculations on direction…..
CHAPTER WORKING NOTES:
MSVs—Kara; TJ; specialized synaptic morph changes.
Tissue cultures lacking astrocytes—how good a model? Lack of synapse
formation in cultures without astrocytes (Ullian, et al., 2001). Moreover, even
when synapses do form, they are functionally immature. Obvious implications on
studies of “synaptic plasticity” in vitro. NOT SURE WE HAVE TIME FOR THIS
NOR IS THIS NECESSARILY CONSISTENT WITH UNDERLYING THEME OF
THE PAPER.
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 DEFINITELY NOT ENOUGH TIME FOR THIS.
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. DONE TO
AN EXTENT, NIX THIS SECTION?