Science Honors Program Neurobiology of Development and...
Transcript of Science Honors Program Neurobiology of Development and...
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Science Honors ProgramNeurobiology of Development and Disease
Ryan [email protected]
Laboratory of Lloyd GreeneColumbia University
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Organization of the Human Brain
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The Central Nervous System (CNS)
• Average human brain: 1350g
• Contains about 85 billion neurons
12-15 billion telencephalic
70 billion cerebellar granule neurons < 1 billion are
brainstem and spinal neurons
At least a thousand different cell types in the brain
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1. Spinal Cord• Divided into four segments: cervical,
thoracic, lumbar, sacral. • Acts as an assimilation, information
processing and relay center between the periphery (skin and skeletal muscles) and the rostral CNS areas (brain).
2. Medula Oblongata• Primary center for autonomic regulation:
digestion, breathing, and heart rate. • Lies rostral of spinal cord.
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3. Pons• Relays information of movement from
the cerebral hemispheres to the cerebellum.
4. Cerebellum• Connected to the brainstem by several
major fiber tracts called peduncles. • Modulates the force and range of
movement. • Involved in the learning of motor skills.
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5. Midbrain• Controls diverse sensory and motor
functions (ie eye movement, coordination of visual/auditory reflexes).
• Thalamus: Functions as the relay center for most sensory modalities arriving at the visual cortex from the rest of the nervous system.
• Hypothalamus: Regulates autonomic, endocrine, and visceral function.
Segregated into two areas: 6. Diencephalon
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7. Cerebral Hemisphere
• Cerebral Cortex:– Divided into 4 lobes– Each lobe mediate specialized
functions. • Basal ganglia: regulation of motor
performance• Hippocampus: short term memory
storage• Amygdaloid nuclei: coordinates
autonomic and endocrine responses of emotional states.
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Lobes of the Cerebral Hemispheres
• Frontal lobe: planning, coordination of planning with motor activity.
• Parietal lobe: somatic sensation, forming a body image, and relating one’s body image with extrapersonal space
• Temporal lobe: hearing, learning, memory and emotion.
• Occipital lobe: vision.
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Hallmarks of early brain science• Greek physician Galen believed that the nervous system were glands
that transmit fluids from the brain and spinal cord to the periphery. • The Italian physiologist Luigi Galvani (late 1700s) discovered that
muscles and nervous tissue produce electricity. A number of clever Germans (DuBois-Reymond, Mueller, von Helmholtz) follow up and demonstrate electrical activity of neurons effect activity of adjecent neurons.
• Pharmacologists (esp Bernard, Ehrlich, Langley) show that drugs recognize specific target receptors on usually on the cell membrane chemical basis of neural communication.
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Franz Joseph Gall• German physician and neuroanatomist• Proposed 3 new theories:
– All behavior emanated from the brain
– Specific functions are controlled by specific cortical areas.
– Each of these areas grew as its function was exercised, therefore, one can interpret areas that are most developed by reading bumps on the skull (phrenology)
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Pierre Flourens
• In 1820 applied Gall’s theory to experimentation.
• By lesioning areas of rabbit and pigeon brains he could find no specific deficit in individual behaviors .
• This led to the concept of the aggregate-field view of the brain all brain regions perform all functions.
“All perceptions, all volitions occupy the same seat in these (cerebral) organs; the faculty of perceiving, of conceiving, of willing merely constitutes therefore a faculty which is essentially one.”
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Pierre Paul Broca
• Suggested that studies to identify localization of behaviors in the brain should be based on clinical lesions and not on bumpy heads.
• 1861 he describes a patient named Leborgne with aphasia (inability to speak). Postmortem analysis of the man yielded a lesion in the posterior prefrontal cortex (now known as Broca’s area).
• Follow up with eight other patients yielded similar results.
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Karl Wernicke
• Described another type of aphasia: the patient could speak but not understand language.
• Identified a lesion in the posterior temporal lobe (now known as Wernicke’s Area).
• Later Wernicke’s area found to be in a larger association cortex that integrates many sensory modalities in to perception.
Broca and Wernicke’s work (along with others) lent evidence for a new model of brain function, the distributed processing specific functions are carried out by specific brain areas.
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Camillo Golgi
• Fervent supporter of “continuity” belief of the nervous system as a syncytium.
• Developed a highly important staining technique (the “black reaction” - la reazione nera) with silver salts that allowed labeling of subsets of neurons.
Drawings from Golgi silver stain technique
Micrograph of a Golgi stain
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Santiago Ramón y Cajal
• Pioneer of the neuron doctrine individual neurons are the signaling units of the nervous system
• Discovered law of dynamic polarization (that neurons receive information on their soma and dendrites and transmit it through their axons)
• Principle of connectional specificity: neurons organize into specific nonrandom networks.
• These discoveries led to the idea of cellular connectionism for a brain model
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Neurons are Highly Polymorphic
• Neurons possess a dizzying arrays of shapes, sizes and characteristics that have been specified by evolution to fulfill their specialized role in the networks they are a part of.
• Different classes of neurons use certain neurotransmitters to propagate their signal downstream in the network. This is a property of their fate.
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Cellular Architecture of a NeuronDendrites: neuronal process that receives information
output from other neurons upstream in the circuit.
Soma: cell body of the neuron.
Axon hillock: proximal (near the soma) region of the axonthat integrates the input in a neuron and triggersfiring of electrical signals.
Axon: long process that transmits electrical signals (actionpotentials) across distances to synaptic terminals
Node of Ranvier: gaps in myelination that boost andmaintain amplitude of the action potential firing.
Myelin sheath: insulation surrounding an axon thatprevents deterioration of the electrical signal.
Synapse: specialized structure by which neurons interfaceand exchange information.
Presynaptic terminal: site for neurotrasmitter release Postsynaptic dendrite: site for capturing signaling
information from an upstream neuron
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Autonomic Effects
• stimulates heartbeat• raises blood pressure • dilates the pupils • dilates the trachea and the
bronchi• stimulates the conversion of
liver glycogen into glucose • shunts blood away from the
skin and viscera to the skeletal muscles, brain, and heart
• inhibits peristalsis in the gastrointestinal (GI) tract
• inhibits contraction of the bladder and rectum
• slowing down of the heartbeat
• lowering of blood pressure • constriction of the pupils • increased blood flow to
the skin and viscera • peristalsis of the GI tract
Sympathetic Nervous System Parasympathetic activation
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Peripheral/Autonomic Nervous System (PNS)
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Contrast between PNS and CNS
• Axon myelinated by Schwann cells
• Regenerative capacity• Either cholinergic
(parasympathetic) or adrenergic/noradrenergic (sympathetic)
• Release neurotransmitter from varicosities in the processes to many postsynaptic targets.
• Axon myelinated by oligodendrocytes
• Regeneration incompetent
• Utilize wide array of neurotransmitters.
• More diverse array of cell types.
• Release neurotransmitter to select postsynaptic targets via synapses.
PNS CNS
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Glia, the other neural cell…
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The Five Kinds of Glia
• Schwann Cell: myelination in the PNS• Oligodendrocyte: myelination in the CNS• Microglia:
– phagocytotic cells– Activated and recruited during injury, infection, and siezure.
• Astrocyte: – establish blood-brain barrier– transport nutrients to neurons– uptake neurotransmitters to enhance transmission of signals– maintain [K+] around neurons to upkeep electrochemical gradient.
• Radial Glia: – function as embryonic neural stem cells. – Act as a scaffold to guild differentiating neurons up to the surface.
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Glia at Work
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Astrocytes Form a Blood-Brain Barrier