Lecture 7 Slides Flashcards
The human brain changes significantly during postnatal life. (Axonal pathfinding, synaptogenesis, death, refinement).
Axons and dendrites in the human cerebral cortex at different stages. Based upon Golgi-stained neurons in the cerebral cortex from individual post-mortem samples of different ages.
The parallel growth of dendritic an axonal branches and the addition of synaptic connections early in life must account for a significant portion of post-natal brain growth, and perhaps provide a substrate for enhanced behavioral capacities.
There is a subsequent decline in synapse numbers during adolescence. This is not surprising if Hebb’s postulate is correct. Accordingly, synaptic connections and related neuronal growth are the ultimate targets of activity dependent change during early postnatal life – initially for progressive construction and then selective elimination of connects.
Progression construction of the brain
During the initial phases, the brain gets larger because of post-natal growth of dendrites, axons and synapse (NOT neurons). During the elimination phase, the brain does continue to grow, reflecting the continued elaboration of the synapses that remain and the neurons that they target.
These events occur alongside the acquisition of sensory and motor abilities, capacity for social interaction, and increasingly sophisticated cognitive behaviours including spoken, signed or written language.
Hebb
The combination of activity dependent modification of connections initially suggested by Hebb and corresponding brain growth and behavioral change during early life must underlie how each individual’s brain ultimately develops to see the challenges of adapting to a dynamic environment.
Hubel and Wiesel
Neurons in the primary visual cortex respond selectively to oriented edges.
Anesthetized animal is fitted with contact lenses to focus the eyes on a screen, where images can be projected. An extracellular electrode records the neuronal responses. Took micro electrode recordings that reported the repossess of individual neurons in the lateral geniculate nucleus and the cortex (in response to various patterns of retinal stimulation).
The responses of neurons in the lateral geniculate nucleus were found to be remarkably similar to those in the retina, with a center-surround receptive field organization and selectivity for luminance increases or decreases.
Effect of early eyelid closure of one eye on the distribution of cortical neurons driven by stimulation of both eyes.
Histograms plot the number of cells that fall into one of the seven collar dominance categories, defined based on the frequency of AP activity elicited from visual cortical neurons following illumination int he revenant eye.
Penlight was shined into both wide-open eyes to elicit responses in the visual cortex.
Group 1 cells are driven only by stimulation of the ipsilateral eye, group 7 the opposite. Group 4 neurons are driven equally well by both eyes.
(A): group one, did not have eyes sewn shut; contralateral vs ipsilateral eyes. No cells that were not responsive to light stimulation in the retina.
(B) One eye of a newborn kitten was closed from 1 week after birth until 2.5 months of age, then opened. Relatively brief deprivation. Light presented to the open but transiently deprived eye elicited no electrical responses in visual cortical neurons. The only visually responsive cells responded to the non-deprived eye. Eye that remained open was uniquely able to drive most cortical cells. The deprived eye had been functionally disconnected from the visual cortex.
(C) Monocular deprivation in adult. The ocular dominance distribution across all cortical layers and the animal’s visual behavior were indistinguishable from normal when tested through the reopened eye.
Implications of kitten eye suture experiment
Sometime between when a kitten’s eyes open and 1 year of age, visual experience determines how the visual cortex is wired with respect to eye dominance. Visual deprivation during the critical period must result in some sort of cortical connectivity changes that influence the functional response properties of individual neurons (neither retinal nor retinogeniculate activity is altered).
Consequences of a short period of monocular deprivation at the height of the critical period in the cat - and implications
Shows that there is a period of susceptibility to visual deprivation => critical period for ocular dominance development.
Mixing of the pathways from the two eyes first occurs in the striate cortex – and implications
(A) Although the LGN (lateral geniculate nucleus) receives input from both eyes, the inputs are segregated in separate layers.
(B) In many species, including most primates, inputs from the two eyes remain segregated in the ocular dominance columns of layer 4. Layer 4 neurons send their axons to other cortical layers; it is at this stage that the information form the two eyes converges onto individual neurons.
(B, C) Physiological demonstration of columnar organization of ocular dominance in primary visual cortex. Cortical neurons vary in strength of their response to the inputs form the two eyes, from complete domination by one eye to equal influence of the two eyes.
Inputs from both eyes are present at the level of the LGN, but contralateral and ipsilateral retinal axons terminate in separate layers so that the individual geniculate neurons are strictly monocular, driven by either the left or right eye but not both. Activity arising from either eye that is conveyed by geniculate axons continues to be segregated at the earliest stages of cortical processing as these axons terminate in alternating eye-specific ocular dominance columns in cortical layer 4. Beyond this point, signals from the two eyes converge.
Ocular dominance columns in layer 4 of the primary visual cortex of an adult macabre– and implications
Illustrates the labeling procedure. Following the transynaptic transport of the radioactive label. Looking at the distribution of ipsilateral, contralateral and retinal ganglion cells axon terminals in the LGN.
Showing the ocular dominance columns; radioactive label is specifically labelling the geniculocortical terminals (synaptic terminals in the visual cortex) corresponding to that eye. Complete ocular dominance is seen in the domains (stripes) in cortical layer 4.
Transneuronal labelling with radioactive amino acids
Ocular dominance columns in layer 4 of primary visual cortex of adult macaque
Terminations from the injection of radioactive amino acids are visible as bright bands on the autoradiogram. Retinal ganglion cell axon terminals as seen in the LGN; geniculocortical terminals related to the infected eye are visible as a pattern of light stripes; section through layer 4 on the plane of the cortex.
Effect of monocular deprivation on the pattern of ocular dominance columns in the macaque – implications
Animals deprived from brith of vision in one eye develop abnormal patterns of ocular dominance stripes in the visual cortex, presumably due to the altered patterns of activity caused by deprivation. The stripes related to the open eye are substantially wider, and the striped representing the deprived eye correspondingly diminished.
Implications: Absence of cortical neurons that respond physiologically to the deprived eye is not simply a result of the relatively inactive inputs withering away; otherwise one would expect to see areas of layer 4 devoid of any thalamic innervation. Instead, inputs from the active, open eye take over some, but not all, of the territory that formerly belonged to the inactive closed eye. These inputs then dominate the physiological responses of the target cortical neurons.
=> competitive interaction.
Competitive interaction
Competitive interaction for post-synaptic space between afferent axons driven by each of the two eyes during the critical period, reminiscent of Hebb’s description of synaptic plasticity but in the context of development.
When an imbalance in visual experience is induced by monocular deprivation, the active eye gains a competitive advantage and replaces many of the synaptic inputs from the closed eye. Even though LGN axons arising from neurons innervated by the closed eye are retained in the cortex (with less extensive terminals and functional synapses), few if any neurons fire AP when light is presented to the deprived eye.
Effects of monocular deprivation on arborizations of LGN axons in the visual cortex
After only a week of monocular deprivation during he critical period, axons terminating in layer 4 of the primary visual cortex from LGN neurons driven by the deprived eye have greatly reduced numbers of branches compared with those from the open eye. Longer periods of deprivation does not result in appreciably larger changes in the arborization of geniculate axons.
The effects of eye closure on the formation of ocular dominance columns.
Top diagrams show the gradual segregation of the terminals of lateral geniculate affronts in layer 4 of the visual cortex under normal conditions vs when one eye has been closed (and closure at different stages of the animal’s development).
Here we see critical periods demonstrated, given that closure at particular weeks but not others results in a drastically different segregation of terminals.
Hebb’s postulate and the development of synaptic inputs.
PostS neuron is shown with two sets of preS inputs, each with a different pattern of electrical activity. Activity patterns, corresponding to AP frequency, are represented by the short vertical bars. 3 correlated inputs at the top are better able to activate the postS cell. These cause the postS cell to fire a pattern of Pas that follows the pattern seen in the input. As a result, the activity of the preS terminals and the postS neuron is highly correlated. Therefore, according to Hebb’s postulate, those synapses are strengthened. The two additional inputs relay a different pattern of activity that is less well correlated with the majority of the activity elicited in the postS cell. These synapses will gradually weaken and are eventually eliminated.
Cooperation; competition; relative activity
Transduction of electrical activity into cellular change via Ca2+ signalling
NMDA-R signalling in the context of the developing NS has been shown to be a key mechanism for the molecular transduction of activity and experience-driven changes during critical periods. Additional ionotropic glutamate receptors, particularly AMPA-R, also establish or reinforce depolarization due to correlated activity.
(A) Summary of the signal transduction essential for critical period synaptic plasticity, 1º at the postS specialization. Excitatory activity (after birth, experience dependent) is proportional to the level of glutamate release from the preS terminal. In turn, glutamate binds to the ionotropic receptors NMDA-R and AMPA-R, as well as to the metabotropic glutamate receptor mGluR. The consequence of NMD-R and AMPA-R activation via glutamate binding is the depolarisation that favours the influx of Ca2+ via the NDMA-R and the initiation of Ca2+ dependent signalling that can influence local cytoskeletal integrity and receptor distribution and stability. This aspect of structural modulation to translate electrical activity to cellular change also includes the modulation of Ca2+-dependent cell adhesion to either maintain or disrupt the relationship between pre and postS sites. Signalling through mGluR activates 2º messenger cascades that rely on mTOR activation to modulate mRNA translation into protein, or to activate ERK signalling, leading to altered nuclear gene transcription.
Transduction of electrical activity into cellular change via Ca2+ signalling pt2
Correlated or sustained activity leads to increased Ca2+ conductances and increased IC Ca2+ [ ], which results in activation of CaMKII or CaMKIV as well as ERK, and their subsequent translocation to the nucleus. ERK and CaMKII/IV then activate Ca2+-regulated transcription factors such as CREB, as well as other chromatin-binding proteins. The target genes for activated CREB may include neurotrophic signals such as BDNF, which when secreted by a cell may help stabilise or promote the growth of active synapses on that cell.
Transduction of electrical activity into cellular change via Ca2+ signalling pt3
Local increases in Ca2+ signalling in distal dendrites due to correlated or sustained activity may lead to local increases in Ca2+ [ ] that modify cytoskeletal elements (actin or tubular based structures), perhaps through the activity of kinases such as CaMKII/IV operating int he cytoplasm rather than the nucleus. Changes in these cytoskeletal elements lead to local changes in dendritic structures. In addition, increased local Ca2+ [ ] may influence local translation of transcripts in the endoplasmic reticulum, including transcripts for NT receptors and other modulators of postS responses. Increased Ca2+ may also influence the trafficking of these proteins, their insertion in the postS membrane, and their interactions ith local scaffolds for cytoplasmic proteins.
Early social deprivation has a profound impact on later brain structure and behaviour
Monkeys isolated when young impacted in terms of brain structure as well as behaviour later in life – tended to be asocial when older.
Shows that there are critical periods for sociality as well as for vision/ocular dominance.
Learning language
A critical period for learning language is demonstrated by the decline in language ability (fluency) of non-native speakers of English as a function of their age upon arrival in the US. The ability to score well on tests of English grammar and vocabulary declines from approx age 7 onwards.
The timing of critical periods varies with brain function
Title
Increased and decreased grey matter volumes parallel critical periods in humans
A composite map of cortical grey matter volume growth and decline (blue/purple). Based on longitudinal MRI scans. There is initial growth of grey matter throughout the cortex, especially in 1º sensory and motor regions, followed by gradual decline. there is some heterogeneity int he timing and rate of decline in 1º sensory and motor versus association areas.
Critical periods and molecular regulators for some neural systems
