Lecture 17 - Experience-Dependent Plasticity PDF

Exam 2 outcomes Exam 1 Average : 72.87 Exam 2 Average: 77.224 Exam 1 Median: 73.73 Exam 2 Median: 77.77 59% saw increased scores from last exam. Experience-dependent plasticity in the developing brain Aims • What is Hebb’s postulate? • What are critical periods? • How does visual deprivation aff...

Exam 2 outcomes Exam 1 Average : 72.87 Exam 2 Average: 77.224 Exam 1 Median: 73.73 Exam 2 Median: 77.77 59% saw increased scores from last exam. Experience-dependent plasticity in the developing brain Aims • What is Hebb’s postulate? • What are critical periods? • How does visual deprivation affect ocular dominance? • What are amblyopia and strabismus? • How can language development be altered? Hebb’s postulate • Fire together, wire together • The coordinated electrical activity of a presynaptic terminal and a postsynaptic neuron strengthens the synaptic connection between them • Uncorrelated activity  connection is gradually weakened & eventually eliminated Phenomena in brain development • Behaviors not initially present in newborns emerge & are shaped by experience throughout early life • There is superior capacity for acquiring complex skills & cognitive abilities during early life • The brain continues to grow after birth • Roughly in parallel with the emergence and acquisition of increasingly complex behaviors and the addition of pre- and post-synaptic processes The brain changes significantly during postnatal life • Construction phase • Post-natal growth of dendrites, axons, and synapses • Elimination phase • Continued elaboration of the synapses that remain Critical periods • The time when experience and the neural activity that reflects that experience have maximal effect on the acquisition or skilled execution of a particular behavior • Parental imprinting in hatchling birds • Certain specific experiences during a sharply restricted time • Critical periods for sensorimotor skills and complex behaviors • End far less abruptly and provide far more time for environmentally acquired experience • Communication skills in songbirds • Language in humans Alarm calls: Vervet monkeys Eagle!! Rudamentary language Particularly for predators Snake!! Newborns need to be trained, they do not come out knowing what an eagle is. They make that sound for anything, but eventually learn to distinguish the sounds for the appropriate thing Seyfarth et al., 1980 Spontaneous activity establishes rudimentary patterns of connectivity in the retinogeniculocortical pathway • Local oscillations, or “waves” of subthreshold activity are essential for shaping circuit networks • Prepare for optimal experience-driven activity • Retinal waves before birth & before eye opening • Each retina independently generates a pattern of waves of electrical activity that moves across large populations of retinal cells in an orderly fashion • Initiated in local retinal cells (amacrine cells)  AP firing by ganglion cells  relayed to LGN  V1 • Coherent in each eye, asynchronous between eyes  competitive interaction between the two eyes Ocular dominance columns in V1 • Competitive interaction between the two eyes • Afferents driven by one eye segregate from those of the other eye • Ocular dominance columns • Alternating series of eyespecific domains in cortical layer 4 • Cells in layer 4 respond strongly or exclusively to stimulation of either the left or right eye • Neurons in layers above and below layer 4 integrate inputs from both the left & right eyes and respond to visual stimuli seen by both eyes I=ipsilateral C=contralateral Effects of visual deprivation • Visual cortical neurons divided into seven ocular dominance groups based on their degree of response to either the contralateral or ipsilateral eye • Group 1 cells driven only by contralateral eye • Group 7 cells driven entirely by ipsilateral eye • Group 4 cells driven equally well by either eye • Normal adult cat: most cells activated to some degree by both eyes • This normal distribution of ocular dominance can be altered by visual experience Effects of visual deprivation • One eye of a kitten sutured closed early in life • Eye was opened at 2.5 months, and kitten matured normally to 38 months • Very few cortical cells could be driven from the deprived (previously sutured) eye • Recordings from the retina and LGN were normal • Deprived eye gets functionally disconnected from the visual cortex • Behaviorally blind in the deprived eye • This amblyopia or “cortical blindness” is permanent Effects of visual deprivation • The same manipulation – closing one eye – performed in adulthood has no effect on the responses of cells in the mature visual cortex • Ocular dominance distribution and visual behavior is indistinguishable from normal when tested through the reopened eye • Sometime between when the kitten’s eyes open and 1 year of age, visual experience determines how the visual cortex is wired with respect to eye dominance Effects of visual deprivation • At the height of the critical period, as little as 3-4 days of eye closure profoundly alters the V1 ocular dominance profile • After this time, deprivation or manipulation has little or no permanent effect Ocular dominance column pattern • In monkeys, the stripe-like pattern of geniculocortical axon terminals in layer 4 that defines ocular dominance columns is already present at birth • This pattern reflects the functional segregation of inputs from the two eyes • Occurs even in the absence of meaningful visual experience • Alternating stripes of roughly equal width Ocular dominance column pattern • Animals deprived from birth of vision in one eye develop abnormal patterns of ocular dominance stripes in V1 • Altered patterns of activity caused by deprivation • Stripes related to the open eye are substantially wider • Stripes representing the deprived eye are correspondingly diminished • Inputs from the active (open) eye take over some – but not all – of the territory that formerly belonged to the inactive (closed) eye • Competitive interaction for post-synaptic space Effects of monocular deprivation on arborizations of LGN axons in the visual cortex Effects of monocular deprivation on arborizations of LGN axons in the visual cortex Why is this important? • Diagnosis and early treatment of amblyopia • Early intervention possible only if an early diagnosis is made • Early diagnoses are not always available before the critical period has closed • Individuals who experienced uncorrected abnormal ocular competition early in life have permanent visual impairment Potential interventions • Rats experienced monocular deprivation from the critical period onset through adulthood • Half were then placed in a completely lightfree environment (“dark exposed”) for 10 days • The other half were maintained in standard illumination conditions • Tested on a visual acuity task Potential interventions • Mechanisms by which dark exposure reactivates cortical synaptic plasticity and permits reactivation of visual capacity remain uncertain • Dark exposure increases the density of spines on visual cortical neuron dendrites • Adult visual cortex retains measureable capacity for plasticity that can improve visual function, if certain conditions are put in place • Dark exposure • Repeated training Strabismus • In humans, amblyopia is most often the result of strabismus • Convergent strabismus: esotropia (“crossed eyes”) • Divergent strabismus: exotropia (“wall eyes”) • These alignment errors both produce double vision • Very common: affect ~ 5% of children • Inputs to the LGN from the optimally aligned eye are competitively advantaged • More V1 territory • Suppressed eye eventually comes to have very low acuity that may render an individual effectively blind in that eye https://www.aoa.org/healthyeyes/eye-and-visionconditions/strabismus?sso=y Manipulating competition • Test the role of correlated activity in driving the competitive postnatal rearrangement of cortical connections • Activity levels in each eye remain the same but the correlations between the two eyes are altered • Cut one of the extraocular muscles in one eye during the critical period • Two eyes are no longer aligned (strabismus) • Objects in the same location in visual space no longer stimulate corresponding points on the two retinas at the same time • Differences in the visually evoked patterns of activity between the two eyes are far greater than normal • Unlike monocular deprivation, the overall amount of activity in each eye remains roughly the same Ocular asynchrony prevents binocular convergence Ocular asynchrony prevents binocular convergence • Input from both eyes remains active but highly asynchronous • Ocular dominance pattern is sharper than normal in layer 4 • Cells in all layers of V1 are driven exclusively by one eye or the other • Prevents binocular interactions in other V1 layers Tuning properties of neurons in primary visual cortex Neurons in lateral geniculate nucleus show similar arrangement as in retina  center-surround receptive fields and selectivity for increases/decreases in luminance In contrast, cells in primary visual cortex respond selectively to oriented bars/edges  The “preferred” orientation is the orientation to which a cell is most responsive Hubel and Wiesel (experiments in late 1950’s; Nobel Prize 1981) Tuning properties of neurons in primary visual cortex Binocular competition during the critical period aligns orientation tuning in binocularly innervated cortical neurons • Prior to eye opening, there is little/no correlation between relatively broad orientation sensitivities in visual cortex neurons driven by both eyes • Fairly low maximal response to preferred orientations • Orientations are dissimilar between the two eyes • Start of critical period: magnitude increases in both eyes, but orientation preference remains dissimilar • Increased correlation of visually evoked stimuli  matching of orientation tuning of the right and left eye inputs to single cortical binocularly driven neurons Binocular competition during the critical period aligns orientation tuning in binocularly innervated cortical neurons • If one eye is closed during the critical period, the matching of orientation tuning of binocular inputs does not occur • Cannot be restored once the closed eye is opened Binocular competition during the critical period aligns orientation tuning in binocularly innervated cortical neurons Cataracts • Render the lens or cornea opaque • Functionally equivalent to monocular deprivation in experimental animals • Left untreated in children, results in irreversible damage to visual acuity in the deprived eye • Largely avoided if treated before 4 months of age • Bilateral cataracts produce less dramatic deficits even if treatment is delayed • Similar to Hubel and Wiesel’s binocular deprivation in experimental animals • Unequal competition during the critical period for normal vision is much more deleterious than the complete disruption of visual input • Individuals monocularly deprived of vision after the close of the critical period are much less compromised Critical periods in other sensory systems Language development • Hearing babies begin babbling at ~ 7 months • Deaf babies exposed to sign language at an early age “babble” with their hands • Regardless of the modality, early experience shapes language behavior Learning language • Critical period for language learning • Decline in fluency of nonnative speakers as a function of age • Children can usually learn to speak a 2nd language without accent and with fluent grammar until about age 7-8 • After this age, performance gradually declines no matter what the extent of practice or exposure Synapse addition and elimination in rhesus monkey cortex Increased and decreased gray matter volumes parallel critical periods in humans • In humans, gray matter volume increases and then decreases in roughly the same way • In contrast, white matter volume increases throughout early childhood and adolescence • Prolonged process of experience-driven construction of cortical circuits is altered in several disorders A behavioral disorder accompanied by altered addition of gray matter volume • Gray matter volume increases more slowly in children with ADHD • The rate of decline is equivalent, although the net result is lower gray matter volume in adults with ADHD Student-led Summary • “What? So what? Now what?” • What? • What did we learn today? • So what? • Why does it matter? How is it useful, relevant, or important? • Now what? • How do we connect this to our previous learning? What else do we need to know? Summary • Experience helps shape neural circuitry and thus determines subsequent behavior • Critical periods • Correlated patterns of activity stabilize concurrently active synaptic connections and weaken/eliminate connections whose activity is divergent • When typical activity patterns are disturbed during the critical period  altered visual cortex connectivity  altered visual function • If not reversed before the end of the critical period, these alterations are difficult or impossible to change