[Neuroscience] Re: motor programs in the brain

Immortalist via neur-sci%40net.bio.net (by reanimater_2000 from yahoo.com)
Mon Aug 6 21:25:19 EST 2007

On Aug 6, 4:52 pm, "rs... from nycap.rr.com" <rs... from nycap.rr.com> wrote:
> Motor programs in the brain
> The first motor program generator (central pattern generator) was
> demonstrated by Wilson in 1961. He showed that an ensemble of neurons
> produced the muscular action required for locust wing action. Since
> then a great deal of work has been done, mostly with invertebrates,
> and with simple circuits. None question that the neural circuits
> involved are constructed by the genome.

> The molecular activity
> involved in such construction of circuitry by the genome is beyond
> present analysis, but many believe that it will be done.

There is much known about this process and you should review some
popular embryology books, even at the public library, these include
the direction of the assembly of these circuits by the genes by,
chemical gradients attracting particular cells to do particular
things, cell multiplication, cell type formation, etc,


Following fertilization there is a period of about 24 hours during
which profound and still poorly understood changes occur. The cell
then divides into two adherent daughter cells and after another 18-24
hour period, becomes a four celled embryo. It seems probable that
until this time, each of the daughter cells maintains the potential to
continue development in its own right and become a separate and
complete individual. This is the source of identical twins, triplets
or quadruplets, when they occur. With successive divisions, this
pluripotential quality is lost and the components of the growing cell
cluster become progressively more specialized.

As the cells continue to divide and adhere to each other through the
8,16, 32 cell stages etc., the cluster begins to resemble a mulberry
and, as a result, this is often referred to as the 'morula' (mulberry)
stage. During the following sequence of divisions, the solid mass of
daughter cells develop an inner cavity, thereby entering the
'blastocyst' (blast, developing; cyst, sac, stage. At one end of the
now hollow, ball-like structure, a cluster of cells grows more rapidly
than those around it, becoming the 'inner cell mass'. This is the
beginning of the embryo. The remainder of the blastocyst will form the
various parts of the embryo/fetus support system, i.e., placenta,
amniotic sac, etc.


Each individual is made up of three different types of tissue.
Ectoderm includes all of the packaging elements of the organism, i.e.,
skin, hair, nails and, interestingly enough, the nervous system.
Mesoderm makes up the the major structural components of the body
including the great muscle masses, both the voluntary muscles which
underlie all of our work, actions and behavior, and the involuntary
muscles which make up the walls of all of our organs such as heart and
blood vessels, respiratory and gastrointestinal systems, and our
bones. Finally the endoderm includes all of the cell systems which
line our organs and vessels.


The inner cell mass originally differentiates into a layer of
primitive (presumptive) ectoderm and an underlying and roughly
parallel-lying layer of endoderm. In the area between these two cell
layers, a few new cells appear, apparently from the underlying
endoderm. These most recent arrivals become the primitive mesoderm.
Their first task is to come together to form a long cylindrical
structure. In doing this, they are recapitulating the earliest event
in the transition from invertebrates to vertebrate forms, a transition
which occurred at least six hundred million years ago. This rod-like
structure is the notochord, the progenitor of the backbone or
vertebral column. We all still carry traces of the old notochord in
our own bodies. Our vertebral column is made up of 32 separate
vertebrae, piled on each other to form our flexible backbone. Between
each vertebra is a small shock absorber or intervertebral disc. In the
center of each of these fibrous disks is a small soft area like a
cherry inside a hard chocolate. This is the nucleus pulposus, the
divided up remnant of our notochord. When we suffer a herniated disc,
it is the nucleus pulposus which has been squeezed out of the
intervertebral disc and is now playing havoc by pressing on one or
more spinal roots. We have literally been 'tripped up' by a vestigial
organ more than half a billion years old!

In the case of the developing embryo, the notochord seems to have a
highly specific "organizing influence" on the primitive ectoderm layer
just above it. Through the release of special chemicals, the overlying
ectoderm is induced to divide more rapidly, forming a thickened mass
called the neural plate. A crease or fold soon appears in this plate.
The crease rapidly deepens and becomes known as the neural groove. The
entire embryo is lengthening as this happens. The neural groove
continues to deepen until its sides, the neural folds, arch over and
fuse with each other forming a short segment of completely enclosed
tube. This newly formed "neural tube" will become the nervous system.
The actual fusion of the walls to form the tube occurs first in the
center of the embryo about midway between front and rear poles of the
still rapidly lengthening little organism. However, you can probably
visualize how the newly formed section of neural tube rapidly begins
to roof over in both a frontward (anterior or rostral) and a backward
(posterior or caudal) direction. It is as if there were two zippers in
the newly formed roof of the developing neural tube. As these zippers
are pulled simultaneously away from each other toward the two ends of
the embryo, the neural folds come together and the neural tube
lengthens progressively in both directions. Finally the neural tube is
almost completely enclosed in both directions, leaving only a small
unroofed portion or opening at each end. These residual openings are
called neuropores and under normal developmental conditions will soon
be closed, thereby forming a complete neural tube. During this process
a front-back polarity has been established in the still-lengthening
embryo. Accordingly, the small unroofed area of the neural tube at the
front end is called the anterior neuropore; the one at the rear end,
the posterior neuropore.


We have already mentioned the remarkable capacity of the developing
nervous system to follow an incredibly complex series of developmental
rules laid down progressively by the genes. Nonetheless, errors occur,
and the roofing over of the neural groove to form the neural tube
represents one point where disturbed development can severely affect
the growing embryo. Incomplete closure of the anterior or posterior
neuropore represents two such developmental errors during the first
trimester which radically alter the future life of the embryo/fetus
and infant.

If the anterior neuropore fails to close, the resulting deficit leads
to varying degrees of incomplete development of the cerebral
hemispheres and brain stem. One of the most frequent and dramatic
resulting anomalies is the fetus which is born without cerebral
hemispheres and usually without any skull above the level of the eyes.
This is the so-called anencephalic child (a- or an- without: cephalon-
brain) Strangely enough, this type of extreme anomaly may come to term
and under some conditions, live for a week or two following birth.
Such a severely deformed infant has only a brain stem (the upward
continuation of the spinal cord within the skull) on which to depend
for its behavior. This takes care of its basic breathing,
cardiovascular, suckling and elimination reflexes. However, little
else is possible for the infant and it usually dies within a few days
or weeks of birth.

If incomplete closure persists at the posterior neuropore, the fetus
will be born with some variant of spina bifida (bifida- split). In the
most severe of these, the posterior portion of the spinal cord is
totally or partially undeveloped and the entire lower back may be
open. Some defects of this sort may be amenable to restorative surgery
while others are not compatible with life. There is a more subtle form
of this anomaly known as spina bifida occulta (occulta- hidden) where
the only residual pathology is a tract or canal, usually of
microscopic size, running between the subdural space surrounding the
lower tip of the spinal cord and the skin of the lower back. Often,
the only sign of such an anomaly is a little patch of hair in the
middle of the lower back just above the beginning of the cleft between
the buttocks. Although usually asymptomatic, this tiny canal can
become infected, usually through trauma, and can form a painful pus-
filled sac known as a pilonidal cyst. Early in World War II, one of
the more frequent surgical procedures was removal of pilonidal cysts
caused by the rough and bouncy ride experienced by soldiers riding in
earlier versions of the famous Army jeep.


With successful closure of the neural tube, the anterior or rostral
(rostral- front) end develops three vesicles which demarcate the
territory for cerebral hemispheres and brain stem. Of these, the first
and third divide once more forming a series of five vesicles which
will become the major portions of the central nervous system within
the skull. These consist of the cerebral hemispheres, diencephalon,
midbrain, pons and cerebellum and medulla oblongata.


The most dramatic phase of development now shifts to the walls of the
neural tube. Here, what is initially a single cell layer of primitive
ectoderm begins to divide very rapidly and will in time form virtually
all of the central nervous system (brain and spinal cord). Packets of
cells 'left over' on each side of the midline, where fusion of the
neural folds initially occurred, are known as neural crest cells.
These will migrate to a number of sites throughout the body of the
developing embryo and form the peripheral nerves, roots, and ganglion
cells of the peripheral nervous system.

We have already mentioned how rapidly cell division occurs in the
walls of the neural tube. The actual process of mitosis (division)
occurs close to the inner edge of the wall. Following this, each
daughter cell moves away from this inner boundary to 'put on weight'
by synthesizing protein, developing DNA and RNA and the various
organelles (tiny intracellular structures necessary for cell life and
energy metabolism) involved in its continued existence. The cell then
moves back toward the inner boundary or multiplication zone where it
undergoes division, thereby producing two more daughter cells and
continuing the process. During this period of rapid growth, the entire
cycle from cell division to cell division may take as little as an
hour and a half. The rapid, geometric increase in the number of these
still-primitive cells results in progressive thickening of the walls
of the neural tube and the enlargements or vesicles at the anterior
end. As these primitive cells continue to divide, subtle decisions
begin to be made as to their fate. Some will become neurons while
others are fated to become glial cells. The way these decisions are
made and the mechanisms involved remain areas of active research
interest. The decisions are of more than academic concern, not only
for the long-term functioning of the nervous system but for the
immediate next step in brain development.


After a period of active replication, some of these primitive daughter
cells initiate the next step in brain development. This involves
leaving the old 'home neighborhood' and moving permanently away from
the inner multiplication zone to the outer edges of the growing wall
of the neural tube. By this process of migration, the walls of the
neural tube thicken selectively, coming to resemble increasingly the
spinal cord, brain stem, cerebellum and cerebral hemispheres of the
mature nervous system. As this thickening occurs, the trip from inner
boundary of the neural tube to the outer portions becomes longer and
increasingly fraught with potential difficulty. For this reason, some
of these daughter cells unselfishly develop into a specialized type of
"rope ladder" configuration, the radial glial guide cells, along which
the primitive nerve cells (neuroblasts) can migrate. A number of these
migrating cells may use the same glial guide cells, literally gliding
up the glial 'rope' one after the other. The migration process is a
complex one, driven and controlled by a number of different chemical
substances. As remarkable as this cooperative process appears, even
more remarkable must be the chemical messages which inform the
migrating neuroblasts where to stop climbing and get off the ladder.

The most dramatic thickening of the original neural tube occurs in the
area of the developing cerebral hemispheres. Here the migratory voyage
is the longest and most complex. There are several principles of
cortical development which have become apparent in the past several
decades and they are worthy of our consideration.


As the primitive neurons or neuroblasts migrate away from the
ventricular border where they have undergone multiplication, they move
outward toward the external border of the thickening neural tube
vesicle (the telencephalon) which is becoming the cortex where most of
the higher level mental activity occurs (perception, cognition, etc.)
The cerebral cortex of most higher forms is made up of six cell
layers. Each layer has its distinct pattern of organization and
connections. During the developmental phase which we are following,
the cells initially move in to form the deepest or sixth layer. Each
successive migration ascends farther, progressively forming more
superficial (fifth, fourth, third second and first) layers beyond the
layer that was initially laid down. Thus each group of migrating cells
must pass through the layers already laid down by the earlier
arrivals, thereby following an inside-out sequence of development.

The later arriving cells appear to migrate out along the same radial
glial guide cells originally used by the earlier immigrants. It is
accordingly very important, that the earlier groups succeed in
"getting off" the glial guide cell before the next wave of immigrant
cells tries to come up and through. We still do not completely
understand how these cells successfully ascend the glial "rope ladder
" nor how they know when to get off the ladder, move a little to the
side and start to form the appropriate cortical layer. But it should
be clear that unless they do release their hold, the next wave of
cells coming up the ladder may not be able to get by on their way to a
more distant destination. When this happens, the ensuing traffic pile
up produces developmental anomalies which can lead to abnormal
neuronal connections and disturbed behavior. Two species of mutant
mice called, "reeler" and "staggerer" because of their bizarre motor
behavior, are believed to result from this type of developmental
abnormality. Similar problems in the growing human fetus may
contribute to the development of certain types of schizophrenia,
temporal lobe epilepsy and, perhaps some forms of dyslexia.

At this point, it can only be speculation, but it is conceivable that
some types of severe character disorders may also reflect
developmental anomalies. A limited group of data suggest that some
individuals with intractable sociopathic deficits show brain changes
which could be interpreted as developing during this period of brain
formation. This is clearly an area which awaits further exploration.


Another curious mechanism which seems to be involved in cortical
development, is the stratagem of developing temporary connections or
holding patterns for incoming, cortex-bound fibers until the proper
target cells are available for them. A large number of significant
fiber connections from structures below the cerebral cortex,
particularly in the thalamus, begin to grow into the primitive cortex
(or the area where it will develop), before the nerve cells have been
able to migrate into their proper layers to receive them. Without
target cells, such fibers would turn away or wither. To avoid this,
groups of special 'decoy' cells are quickly sent into position before
the main migrations begin. One group of decoy neurons locates itself
at what will be the margin between the the cortical or gray matter,
and the underlying white (fiber-rich) matter. A second group of decoys
lines up at the outermost edge of the neural tube wall, at what will
be the most superficial layer of the cortex. These serve as temporary
targets for the incoming fibers which enthusiastically establish
synaptic connections with them. Several weeks later when the great
neuroblast migrations have been successfully accomplished, these decoy
cells unselfishly disappear, a process which is fascinating in its own
right and is now under investigation. The fibers which have been
synaptically attached to them are released and are now attracted to a
more appropriate, and permanent, set of target cells. This remarkable
sequence of processes culminating in a 'change of partners' and the
establishment of more definitive cortical connections is also subject
to error and the results may include a number of major and minor
cognitive and emotional disorders which will show up at various stages
in the life of the individual. We are only at the beginning of our
understanding of these complex phenomena but certain types of dyslexia
may be one of the results of problems during this change of cortical


Once the primitive migrating nerve cells have reached their final
position, they begin to develop extensions from their cell bodies.
These will progressively become longer and form the two major types of
processes or branches which characterize almost all neurons. Dendritic
branches will emerge from many points along the cell body. In the case
of most cortical cells, these will become apical and basilar dendrite
branches, depending on whether they emerge at the apical end of the
somewhat triangular (pyramidal) shaped cell or at the bases. The
former will lengthen and grow toward the surface while the latter will
branch more profusely and grow to the sides (laterally) and/or
somewhat deeper into the cortex. As dendritic branches multiply, they
provide an increasing surface area for fiber terminals (synaptic
terminals) from other neurons. In general, the larger the number of
neuronal connections, the richer the possibilities for neural, and
therefore cognitive activity.

The second major type of cell extension, the axon, will set out on a
journey of variable length to establish connections with many other
neurons, some adjacent to the cell body of origin, others quite
distant. Imagine how far an axon must migrate from the cortex if its
target area is the lower spinal cord of a basketball player! The
distance may be as much as five feet!

One of the more interesting pathways which must be developed during
the late prenatal and early postnatal period is the one which crosses
from one hemisphere to the other and connects similar (mirror image)
point on the two hemispheres. This massive bundle, called the corpus
callosum, exerts powerful though subtle effects on the cortex and
special modes of examination are necessary to reveal them. The two
hemispheres have differing, though complementary, roles and it has
been speculated that the corpus callosum facilitates the interaction
of these effects. For example, for most of us, specific portions of
the left hemisphere (Broca's and Wernicke's areas) are primarily
responsible for the semantic and computational aspects of language.
Corresponding areas of the right hemisphere are involved in the
emotional and prosodic activities and the interweaving of these two
facets of language behavior make for interesting and comprehensible
narration. If activity of the right hemisphere and its interaction
with the left is compromised, either by cortical damage (e.g. a
stroke) or by surgical interruption of the corpus callosal fibers,
this relationship breaks down. Speech then sounds mechanical and flat,
without personal warmth and emotion.


A significant aspect of brain development is the continued growth of
myelin sheaths around the axons of the cerebral cortex. Myelin is a
fatty substance which is deposited around many (though not all) axons
as an insulating sheath. Its presence allows conduction of nerve
impulses to occur from ten to one hundred times as rapidly as would
occur along a non-myelinated axon. Since this obviously increases the
efficiency of the axon system (just as increased computing speed
enhances the efficiency of a computer), the development of axonal
sheaths are taken as a measure of increasing maturity of the neural
system involved. Myelin sheath development, or myelinization as it is
called, has a rather well recognized time table in the cerebral
hemispheres. Fibers serving the primary sensory (touch, vision,
audition etc.) and motor areas are myelinated shortly after birth
while those which are involved with more complex associative and
cognitive functions myelinate later. It is generally believed that
fiber systems of the prefrontal lobes (executive functions,
intentions, future planning, etc.) are among the latest to myelinate,
a process that may go on into young adulthood.


The elaborate ensembles of neurons, their dendritic branches, and
their projective axons communicate via a myriad of connections known
as synapses. Each synapse is a point of contiguity (but not
continuity) between two neural elements The most usual elements which
form synaptic connections are axon terminals with either dendrites or
cell bodies although other combinations are possible. In the vast
majority of these synapses, small amounts of chemicals
(neurotransmitters) are released, crossing the infinitesimal gap
between the two elements, thereby carrying the neural message to the
next element. Tens of thousands of synapses may cover the dendrites
and cell body surface of a single neuron. From this you can easily see
that there are enormous numbers of synapses in the entire nervous
system, probably trillions! There may be as many as one hundred
neurotransmitters and neuromodulators associated with these synapses
providing a vast range of possible interaction patterns at these

The process of synapse formation probably starts in the mid or late
second trimester and continues during the life of the individual.
Careful ultramicroscopic studies show that synapse formation proceeds
at its highest rate during the first 6-8 years of postnatal life, then
plateaus and begins to decrease with the onset of puberty. This
process of numerical decrease can be thought of as a pruning process
in which excess or unwanted connections are discarded. During the
first 6-10 years of life, the young individual undoubtedly achieves
the highest density of synapses per unit volume of neural tissue (and
the highest level of cortical glucose metabolism as revealed by PET
scans) that he/she will ever have. This is also a period of enormous
information input and acquisition, social, environmental, linguistic,
etc. The growing brain may well be in its most sponge-like phase of
learning as the child becomes acquainted with the endless range of
symbols, rules, facts and behaviors that make it a member of its


We have already suggested that during much of the embryonic and fetal
stages of life, genetic influences are of primary significance in
development. It must also be realized, however, that the complexity of
organization and connections of the nervous system far exceeds the
capacity of the genome to specify each cell location, axon trajectory
and connection. Instead, a very wide range of diffusible substances
and markers are generated at appropriate times by primitive neural
components as well as adnexal tissue. These directly affect certain
classes of cells or processes, and facilitate the organization and
development of the growing system. For instance, the young notochord
seems to release factors which stimulate the overlying ectoderm to
thicken and invaginate, thereby beginning formation of the neural
tube. A little later, cells in the ventral portion of the developing
neural tube release factors which specifically direct the trajectory
of axons of primitive spinal neurons, thereby initiating the
development of the long ascending sensory tracts as well as the
peripherally projecting ventral roots. Many such axons, upon reaching
their general target zones, carry retrograde substances from these
areas back to the cell body of origin, thereby further refining the
patterning and terminal distribution of these projecting elements.
Thus the local chemical milieu works in complementary fashion with
genetic plans to specify central nervous system organization.

A broad range of exogenous factors are also involved, including the
health and nutrition of the mother and possible contact with
potentially toxic substances (e.g. tobacco, alcohol and other drugs of
abuse, certain viruses, etc.) The local dynamic mechanisms of
intrauterine life may also be significant, a fact especially
noticeable in the case of multiple births where intrauterine position
may markedly affect the size and vigor of the newborn. Even the
maternal state of mind may be significant, a factor long recognized in
the widespread 'old wives' tale' that the infant will bear the visible
imprint of an object that frightens its mother during her pregnancy.
In a more positive vein, Japanese mothers think happy thoughts
(taikyo) during pregnancy to ensure the health and well-being of their
infant. Recent data suggest that newborn infants are more likely to
respond to sound combinations (words) characteristic of the mother's
language than to those of a foreign tongue. By implication, the unborn
fetus, especially in the third trimester, may already be sensitive to
stimuli in the maternal external environment.

The effects of genetic and epigenetic factors are thus inextricably
mingled, from the earliest stages of embryonic development. The
remarkable combination of gene-controlled factors, some of them
conserved for over a billion years, together with an enormous range of
idiosyncratic factors, both internal and external, help account for
the uniqueness of each individual.

About the Author: Arnold B. Scheibel, MD, is professor of Neurobiology
and Psychiatry and former Director of the Brain Research Institute,
UCLA Medical Center, Los Angeles, CA.


> In vertebrates, the circuitry largely defies analysis, being
> exemplified by populations rather than by individual neurons.
> Here is a list of the major motor pattern generators and their
> approximate location within the central nervous system; all cribbed
> from Larry Swanson.
> Breathing: ventral medulla/upper cervical cord.
> Orofaciopharyngeal movements; facial expression, vocalization,
> licking, chewing, and swallowing: parvicellular reticular nucleus
> (dorsolateral hindbrain).
> Reaching, grasping, and manipulating: cervical enlargement (spinal
> cord).
> Orienting movements;
>      Eyes (oculomotor): dorsal midbrain reticular core.
>      Head and neck: cervical spinal cord.
> Posture: spinal cord.
> Locomotion: spinal cord.
> Some list! Since none seem to question that invertebrate motor pattern
> generators are constructed by the genome, why should we question
> similar construction by the genome in vertebrates (including man, of
> course). The shift from individual neurons to populations of neurons
> is fundamentally trivial. Also trivial (except to anatomists) is to
> extend the "brain" to include the spinal cord. I so do.
> I like to think that a human lifetime can be seen as the genome
> interacting with the environment. Many bridle at such a notion. They
> want to include something from the soul (spirit, essence, psyche,
> mind, consciousness, awareness, intelligence, intellect, mentality,
> self, individuality, persona, personality, conscious mental field,
> self awareness, sentience, executive function), but that is what I
> see.
> Motor pattern generators were learned by the genome during four and a
> half billion years of random mutations; nothing is learned after
> conception. Any mutations acquired during meiosis will be passed on to
> the next generation. We are born with a set of motor pattern
> generators. All motor acts follow from these generators. Specifically,
> all phonemes are produced individually from generators. Man can learn
> initiation, variation, control, and expression of a generator, but not
> the generator itself.
> Man does not "learn" to walk. The walking circuitry in his brain
> matures, and he walks. The environment alters the expression of the
> locomotion generator so the brain (following the rules of neural
> alteration as set up by the genome, enables the organism to get over
> the ground.
> Man's brain matures. In his second year, man starts s to babble (baby
> talk). He does not learn to babble. He just takes pleasure in
> initiating the phoneme generators. Later, then environment will cause
> him to sequence the phoneme generators. He will "learn" a language.
> All, not some--but all, motor acts proceed from the initiation of
> motor program generators.
> The activity of a motor program generator can be liked to a player
> piano. The holes in the piano roll are the generator. As the roll is
> unrolled, air passes through the holes, passes through tubes, and
> actuates the key mechanisms. Music ensues. The pulses of air, passing
> through the tubes, make up an abstract entity that we may call a
> "program".
> Similarly, a motor program generator is activated. Beautifully
> sequenced neural pulses (a motor program) flow through brain circuitry
> until they reach motor neurons. A motor act ensues.
> En route, the motor program flows through the ventral anterior-ventral
> lateral complex of the thalamus. Here the motor program is subject to
> the inhibitive influence of the thalamic reticular nucleus. If the
> program is halted (inhibited), the organism pauses. This pause is
> generally called thinking, or hesitating. I intend to speak more of
> thinking in a subsequent post.
> Ray Scanlon

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