Critical periods in development - “nature” vs. “nurture” Raghav Rajan Bio 334 – Neurobiology I August 29th 2013 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Bio 334 - Neurobiology I - Critical periods in development The story so far ..... Neural tissue is induced during gastrulation Neurons differentiate from precursor cells Gradients of signaling molecules pattern the neural tissue into different parts Axons of neurons find their way to specific partners Neurons form connections with each other and with muscles On a larger scale, maps form within the brain All this so far, is largely driven by genes - “nature” What about “nurture”? How important is sensory experience? 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

There exist “critical” or “sensitive” periods during development Critical period – A strict time window during which experience provides information that is essential for normal development and permanently alters performance. Sensitive period – A limited time during development, during which the effect of experience on brain function is particularly strong http://www.cerebromente.org.br/n14/experimento/lorenz/index-lorenz.html 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

During this period, experience can refine synaptic connections Sensory experience in early life is extremely important and can shape the nervous system While the nervous system continues to be plastic later on, experience does not have as great as influence Visual system Auditory system Song learning in songbirds 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Bio 334 - Neurobiology I - Critical periods in development Donald Hebb proposed Hebbian plasticity rules - “Fire together, wire together” Such synapses are called Hebbian synapses If a pre-synaptic neuron can make the post- synaptic neuron fire repeatedly, those connections are strengthened Conversely, connections that are not effective are lost 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Mark F Bear, Barry W Connors, Michael A Paradiso. Neuroscience: Exploring the brain (2007) – Chapter 23

Visual perception is shaped by early experience People with congenital cataracts (opaque covering of lens) – impaired vision from birth Cataracts typically removed between 10 and 20 years of age Have difficulty perceiving shape and form One form of plasticity that has been extensively studied is OCULAR DOMINANCE PLASTICITY 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Monocular and binocular zones in the visual field Depending on the placement of the eyes, the size of individual zones can vary Kandel, Schwartz and Jessell, Principles of Neural Science Chapter 27 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Bio 334 - Neurobiology I - Critical periods in development In primary visual cortex, eye specific inputs are segregated in layer 4 Normal primary visual cortex has ocular dominance columns – i.e. each column is dominated by input from one of the two eyes Cells outside of layer 4 receive input from both eyes 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Kandel, Schwartz and Jessell, Principles of Neural Science – Chapter 56

Bio 334 - Neurobiology I - Critical periods in development Most cells in monkey primary visual cortex (outside of layer 4) are responsive to stimuli in either eye Only cells in the binocular zone have been considered 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Kandel, Schwartz and Jessell, Principles of Neural Science – Chapter 56

Bio 334 - Neurobiology I - Critical periods in development Most cat V1 cells (outside of layer 4) are binocular – respond to both eyes All expts. in the binocular zone only All expts. in the binocular zone only 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9

Bio 334 - Neurobiology I - Critical periods in development Monocular deprivation results in more responses to the non-deprived eye One eye kept shut for about 2 months after birth Recordings immediately after eyelid is opened LGN responds to deprived eye, although area occupied is smaller 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9

Does disuse lead to loss of connections? Monocular deprivation results in loss of connections from the deprived eye – could be due to disuse What happens during binocular deprivation? Do all cells become unresponsive? 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Bio 334 - Neurobiology I - Critical periods in development Surprisingly binocular deprivation does not alter the ocular dominance histogram A good fraction of cells are unresponsive to light Of the responsive cells, a lot of them show abnormal responses 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9

Competition hypothesis emerges Maybe connections from both eyes compete with each other in cortex Retinal synapses in LGN are not affected by deprivation because they're monocular In the cortex, monocular deprivation result in active afferents from one eye and lower activity from other eye – latter at a disadvantage Strabismus to test the hypotheis Misalignment of eyes 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Organization of binocular inputs Corresponding points in the two retinas receiving inputs from the same location project to nearby locations in layer 4 Strabismus affects this Normally input from both eyes will be active at the same time Not so in strabismus http://www.answers.com/topic/visual-system-organization. Fig. 5 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development

Bio 334 - Neurobiology I - Critical periods in development Kittens raised with aritificial strabismus have very few binocular neurons Misalignment of eyes induced by surgery Visual stimulus does not fall on corresponding portions of the retina Cortical neurons are rarely activated by both eyes at the same time Very few binocular neurons – results later in poor depth perception 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9

Segregation of eye-specific inputs in layer 4 develops after birth 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9

Even horizontal connections are influenced by experience Normally horizontal connections connect columns with different ocular preference Not so, even after two days of strabismus 29th August 2013 Bio 334 - Neurobiology I - Critical periods in development Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 9