Early Experience and Developmental Learning. Overview. Increasing differentiation of areas of cortex Infant is born during height of brain development Tertiary sulci develop from 1 month before to 12 months after birth. Four (very brief) Levels of Brain Development. Creation of a tube.
Thompson, 2001, p. 29
Time-lapse imaging of synapse elimination
Two neuromuscular junctions (NM1 and NMJ2) were viewed in vivo on postnatal days 7, 8, and 9.
Myelin is an electrical insulator sheath wrapped around axons
Oligodendrocytes produce myelin on CNS axons
Schwann cells produce myelin on PNS axons
Short gaps in myelin along axons called nodes of Ranvier
Myelin’s function is to speed action potential propagation down long axons
Each oligodendrocyte has several
processes, each of which produces
a myelin sheath on a different axon
Schwann cells each form only a
single myelin sheath
OF PROCESS LEADING EDGE AROUND AXON
While the leading glial process continues to encircle the axon,
the earlier-formed loops undergo compaction
to form the contact myelin sheath
Electron microscopy at
very high magnification
major dense lines and
PLP is the most abundant protein in CNS myelin
P0 is the most abundant protein in PNS myelin
SODIUM CHANNELS ONLY AT NODES
AT VERY HIGH DENSITY
Action potential at one point along unmyelinated axon produces current that only
propagates short distance along axon, since current is diverted through channels
in axon membrane. So action potential can only next occur short distance away
Myelin reduces effective conductance and capacitance of
internodal axon membrane.
Action potential at node of Ranvier produces current that propagates
0.5-5 mm to next node of Ranvier, generating next action potential
NODE-INTERNODE PERIAXONAL RESISTANCE WHICH
ELECTRICALLY ISOLATES INTERNODAL MEMBRANE
Tight junctions between
Only 20 Angstrom gap between
mature paranodal loop
and axonal membrane
Rparanode >>>> Raxial & Rleak
MOST MATURE MYELINATED AXONS
Myelinated axons conduct action potentials at ~ 50 mm/msec
Total refractory period of nodal Na+channels after inactivation
is ~ 5 msec.
Therefore, by the time Na+channels return to rest after an action potential, the spike has propagated 25 cm away
(which is terminated in most cases)
K+channel inhibition in mature myelinated fibers
does not alter conduction or promote misfiring.
PROTEIN CLUSTERS DURING MYELINATION
“SHIVERER” mutant mouse has almost
complete absence of myelination,
due to a failure of precursor cells
to differentiate into oligodendrocytes
Other mutations which impair
myelination are mutations in the
major protein components of
the myelin sheath
Similarly, structural mutations in PNS myelin protein genes
cause defective myelination of the PNS
Anatomy and physiology are especially sensitive to modulation by experience.
An extreme form of Sensitive Period.
Appropriate expression is essential for the normal development of a pathway or set of connections (and after this period, it cannot be repaired).
e.g., There was a critical period for the formation of ocular dominance columns, based on neuronal activity/input from both spontaneous firing and visual inputs from the eyes.
If appropriate information is not received during the critical period (from experience), this pathway never attains the ability to process information in a normal fashion, and as a result, perception or behavior can be permanently impaired.
E.g., development of appropriate social and emotional responses to others.
E.g., development of language skills in humans.
- a “map” of auditory space is developed in the midbrain of the barn owl.
- This map integrates auditory and visual info so that movements of the eyes and head can be oriented towards auditory stimuli (and catch mice and rats!).
To create a map of auditory space, the midbrain nucleus has to learn (of inferior colliculus) spatial cues based on auditory signals it receives from the 2 ears.
Differences in timing and in the level (and pitch) between the 2 ears.
Why are these things not just genetically encoded?
Individual differences in size, shape of head, sensations and speed of head movement, etc.
In young animals, this plasticity allows the pathway to respond and adjust to change or disruptions (e.g., growth, damage to ear, etc.).
Tuning of inferior colliculus neurons is adjusted in response to visual cues.
The location of plasticity is the ICX (external nucleus of the inferior colliculus).
If a stable shift in visual field occurs during the critical period (i.e., owls raised with prisms over their eyes), the auditory receptor field of the icx will realign with the shifted visual field.
Now, the owl will have (correctly coordinated visual/auditory stimuli with the prisms on).
The sensitive period for the owl, during which large shifts can occur, is throughout juvenile life (until reaching sexual maturity).
The experience induces the growth and elaboration of axons into the icx to sites where they can support appropriate responses.
This response depends upon activation of NMDA receptors (involved in plasticity).
Note: in our example, the power of genetically programmed pattern is still great (though an adult owl cannot adjust to a large shift in visual field, one that has been shifted can return to normal in the adult (over a period of weeks) when the prisms are removed.
A special form of communication developed by birds to i.d. their own, defend territories, or attract mates.
Birdsong is complex and has a periodic structure (like music).
“Dialects” or varieties of song can specify a geographic area, where the basic song structure is common to a species.
Song is developed by a combination of genetic instructions and learning (early experiences). The latter often takes place during a critical period.
*How can the extent of the critical period be determined in a species?
[raise birds in acoustic isolation and expose them to song for brief periods at different points of development]
“Isolate song”: a flat, species-specific pattern with complexity that a bird can develop if raised in isolation during the critical period.
“Developmental song”: abnormal pattern developed in a bird that is unable to hear itself and get auditory feedback during critical period.
2) Shows importance of a critical period during song memorization (learning songs of conspecifics: 2-8 weeks).
3) Illustrates importance of critical period during vocal learning (bird hears and evaluates his own song so that it matches the memorized song pattern).
[auditory feedback is essential for shaping the pattern of connectivity in the song-production pathway]
Importance of genetic background for the types of patterns that can develop:
- note isolate song (earlier)
- what does a baby bird develop when raised with an alien (other species) birdsong during the critical period for memorization?
[genetically detrimental “filters” within pathway are responsible for song memorization].
If too distinct from normal, isolate song develops.
Regarding song memorization, the critical period is closed after the appropriate stimuli have been received.
After 8 weeks plasticity decreases; So, stimulus must be prolonged and rich (i.e., live bird and not a recording) for any memorization to occur.
Closure of critical period and decreased plasticity are also related to sexual maturity.
*What happens if a bird receives testosterone early? (song is fixed in “immature” state).
*What happens if bird is castrated prior to learning to sing?
[song production inconsistencies and unstable for rest of life – critical period never closes?]
Neural Pathway for Song Learning
Still an active area of research
We know a little regarding song production in species when only males sing (*how is this studied?)
Song System – 2 groups of nuclei:
Motor – posterior forebrain: song production
Feedback – anterior forebrain: oral learning
Posterior pathway: - necessary for products of learned sounds. Higher visual center (HVC) RA arhistriatum hypoglossal nucleus:
motor neurons centrally
Anterior pathway: neurons respond maximally to bird’s own song.
HVC “area X” DCM (a thalamic nucleus) LMAN (lateral magnocellular nuc of ant striatum)
A lesion in LMAN during critical learning period “freezes” song much like early testosterone.
However, lesions in adult birds after learning is complete have zero effect.
LMAN then sends input to RA hypoglossal n. muscles mediated by NMDA receptors.
These synapses will compete selectively and several will be eliminated just prior to closure of critical period (as sex hormones rise).
Learning of cues through i.d. a parent – important for survival involves learning multiple sensory cues that i.d. the parent (visual, auditory, olfactory, etc.) during brief critical periods.
Recall the classic experiment by Konrad Lorenz (“mother goose”).
Critical periods can be brief and can begin shortly before birth in some species.
What happens if baby is in isolation during critical period? [never responds appropriately to social signals from members of its own species].
What happens when raised by another species?
What is the genetic filter here?
During the (critical) imprinting period, a duck will choose a duck over another species, or the closest equivalent (i.e., goose > human).
One Neural Path
Auditory stem nucleus of anti forebrain activated as in previous examples of selective elimination of inputs occurs during late critical period in response to experience.
Ability to “fuse” the image from 2 eyes to create a 3-D image with depth.
The consequence of visual inputs onto neurons of the visual cortex is guided by early experience.
A critical period exists, during which monocular deprivation can prevent the development of stereoscopic vision.
Review the development of the ocular dominance columns for the projection of LGN to Layer IV of visual ctx.
Equal input from both eyes equally wide columns with competition based on neural activity:
If 1 eye is occluded, open eyes inputs are pruned and activity of majority of visual ctx is driven by LGN afferents from normal eye.
*Competition is driven by:
amount of neural activity
degree of synchrony
Therefore, the stimulation of both optic nerves with equal but asynchronous stimuli one dominating , and impaired binocular vision.
Amount and synchrony of synaptic activation shapes the synaptic function and architecture by adjustments in synaptic strength through a process depending on activation of NMDA receptors: LTP.
*Rats: This dual process is not as rapid and plastic as the other examples we have reviewed. Disruption are not completely universal during critical period and patterns are not as ‘pre-set’.