Unit 1: Neuroanatomy Flashcards
(190 cards)
1
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Neurobiology
A
Study of cells of the nervous system and the organization of these cells into functional circuits that process information and mediate behavior
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Nissl Stain
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Basic dyes stain nuclei of all cells as well as clumps surrounding the nuclei of neurons. Stain reacts with nucleic acids. Distinguishes between neurons and glia and arrangement of neurons
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Golgi Stain
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Silver chromate solution makes a small percentage of neurons become darkly colored
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Grey matter
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On surface in brain, neurons and synapses
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White matter
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Connects grey matter, myelinated, axons
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Ben Franklin (1751)
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Experiments and observations on electricity
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Luigi Galvani and Emil du Bois-Reymond (1800)
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Electrical stimulation of nerves causes muscle movement
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Charles Bell and Francois Magendie (1810)
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Dorsal roots of spinal cord carry sensory info into brain, ventral roots carry motor info out to muscles
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Marie-Jean Pierre Flourens (1823)
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Cerebrum: sensation/perception
Cerebellum: motor coordination (does not initiate movement but does it well)
Localization theory
Cut birds brains
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Paul Broca (1861)
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Left frontal lobe is responsible for the production of speech
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Charles Darwin (1859)
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Common behaviors: common mechanisms
Specialized traits: specialized mechanisms
Nervous system of different species evolved from common ancestors by natural selection
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Reticular theory
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Nerves are continuous (old theory)
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Neuron doctrine
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Nerve cells are separate, distinct entities (new theory). They communicate by contact, not continuity
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Microscopes (early 1800s)
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First opportunity to examine tissue at high magnification
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Theodore Schwann (1839)
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All tissues are composed of microscopic units called cells
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Camilo Golgi (1873)
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Soaked brains in silver chromate solution=Golgi stain=small percentage of neurons become darkly colored in their entirety (based on complexity, argued for reticular theory)
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Santiago Ramon y Cajal (1900)
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Used Golgi methods to draw out circuitry in many regions of the brain (advocate of neuron doctrine)
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Electron microscope (1950s)
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Uses electron beam instead of light to form better images, neurons in contact but no continuity (neuron doctrine wins)
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Neuron
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Dendrites (receive inputs from other neurons) –> soma (processes info) –> axon (transmits output of processing to other neurons)
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How do neurons differ from other cells? (2)
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- They stop dividing after birth
2. They have dendrites and axons (specialized structures designed to receive and transmit info)
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What distinguishes cells from each other?
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Specific parts of DNA that are used to assemble the cell (genes). DNA within every cell in the body is the same
22
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Where does protein synthesis occur?
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Ribosomes in cytoplasm. Ribosomes can be freely floating in cytosol or bound to rough ER
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What is binding regulated by?
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Transcription factors
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Where are proteins that are synthesized in free ribosomes destined for?
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Internal structures such as the cytosol, nucleus, and mitochondria
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Where are proteins that are synthesized on rough ER destined for?
Inserted into plasma membrane or enclosed in vesicles to be released from neurons as neurotransmitters
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What does the Golgi apparatus do?
Site of extensive "post-translational" chemical processing of proteins released from rough ER, also directs transmembrane and secretory proteins to their destination (soma, dendrites, or axon)
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Mitochondria
Site of cellular respiration, import pyruvic acid oxygen, Krebs cycle and ETC, produces ATP
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Neuronal Membrane
Barrier to enclose cytoplasm and exclude certain substances, phospholipid bilayer
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What can DNA microarrays be used for?
Determine which genes are expressed uniquely in neurons, or which genes are more or less abundant in normal vs diseases brains
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Important properties of genetic engineering (2)
1. Target specificity (strand break)
| 2. Temporal control (inducible drugs)
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Neurite
Includes many dendrites and one axon, designed to receive and transmit information
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Axon characteristics
Constant radius, long and branch at right angles, have myelin sheath and transmit electro-chemical signals
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Dendrite characteristics
Taper off in shape, shorter and branch profusely at all angles, no myelin sheath, receive electro-chemical signals
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Roles of cytoskeleton
Gives shape to neuron (changes), mechanical support, aids in transport, allows cells to migrate, segregated chromosomes during cell division
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What is tau?
A protein that allows for change in microtubules and helps neuron change shape continually
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How is axon different from soma? (2)
1. No ribosomes in axon= no protein synthesis
| 2. Protein composition of axonal membrane is fundamentally different than soma
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How is the cytoplasm in the axon terminal different than in the axon proper? (3)
1. Microtubules do not extend into terminal
2. Terminal contains numerous small bubbles called synaptic vesicles
3. Terminal contains many mitochondria (high energy needs because of long transport)
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What way does information flow?
Pre to post synaptic side of synapse (axon terminal of one neuron to dendrite or soma of the next cell)
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Why is axoplasmic transport needed?
Axons lack ribosomes so proteins are made in soma and shipped to axon, fast transport is in the microtubules
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Anterograde
Towards the terminal: kinesin
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Retrograde
Back to the soma: dynein
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Tract Tracing
Used to trace the paths of axons
Anterograde: trace axons projecting away from cell bodies
Retrograde: trace axons projecting into area of cell bodies
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Dendritic spines
Isolate various chemical reactions that are triggered by some type of synaptic activity, has free ribosomes in base of spine=protein synthesis
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Glia cells
Outnumbers neurons 5:1, provides structure/metabolic support to neurons
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Oligodendrocytes
Extensions rich in myelin, create myelin sheaths around axons in CNS
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Schwann Cells
Similar in function of oligodendrocytes, but in PNS, can guide axonal regeneration
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Microglia
Involved in response to injury or disease, exist in state of rest until activated
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Astrocytes
Largest glia, star-shaped, many functions:
Form barrier to unwanted substances entering brain, control blood flow to neurons, maintain proper chemical state outside of neurons, removes waste, surround synapses and can modify neuronal signals, send nutrients (glucose) to neurons, digests old neuronal parts, secrets neurotransmitters and glialtransmitters
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Central Nervous System Function
Interprets sensory input, initiates movement, and mediates complex cognitive processes
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Peripheral Nervous System Function
Serves to bring sensory info into CNS (afferents) and carry motor signals out from CNS (efferents)
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Rostral
Anterior- towards the front/nose
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Caudal
Posterior- towards the back/tail
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Ipsilateral
Structures on same side of head
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Contralateral
Structures on opposite side of head
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Sagittal cut
Left vs right
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Horizontal (transverse) cut
Top vs bottom
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Frontal (coronal) cut
Front vs back
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Cross-section cut
Cut at right angle to spinal cord
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3 major fissures (large grooves) in cerebrum
1. Longitudinal 2. Central 2. Lateral
Divides hemisphere into four lobes: frontal, parietal, temporal, occipital
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3 large gyri (bumps) in cerebrum
1. Precentral 2. Postcentral 3. Superior temporal
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Commissures
Fiber tracts in cerebral hemispheres, largest is corpus callosum
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3 different areas of cerebrum
1. Outer area of neuronal cell bodies (grey matter of cerebral cortex) 2. Inner area of myelinated axons (white matter) 3. Subcortical areas of grey matter
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Ventricular system
Fluid-filled caverns and canals
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Folium
Ridge or gyrus in the cerebellum
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Diencephalon
Either side of third ventricle
1. Thalamus
2. Hypothalamus
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Midbrain
Cerebral aqueduct
1. Tectum
2. Tegmentum
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Pons
Below 4th ventricle
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Medulla
Below 4th ventricle, continuous with spinal cord
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Computer tomography (CT)
Measures opacity to x-rays
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Magnetic Resonance Imaging (MRI)
Measures hydrogen atom response to magnetic fields
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Diffusion Tensor Imaging (DTI)
Used to visualize large bundles of axons (track movement)
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Positron Emission Tomography (PET)
Inject radioactive substance, have subject perform behavior, scan horizontal slice in brain
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Functional Magnetic Resonance Imaging (fMRI)
No substance injected, have subject perform behavior, scan brain for de/oxygenated hemoglobin
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Regions of the vertebral column (4)
1. Cervical (8) 2. Thoracic (12) 3. Lumbar (5) 4. Sacral (5)
1 coccygeal
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Dorsal root in spinal cord
Brings sensory information into the spinal cord (afferent), cell bodies in dorsal root ganglion
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Ventral root in spinal cord
Carries motor information away from spinal cord (efferent), somas in cord
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Sensory examples
Unipolar, dorsal, ascending, afferent
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Motor examples
Ventral, descending, efferent
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How do spinal cord areas differ than in the brain?
Grey matter is inside in H shape rather than outside. Outer area is white matter
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Spinal cord grey matter
Divided into dorsal and ventral horns, each contains prominent nuclear groups
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Meninges
Protects the brain and spinal cord from coming into contact with the bones (skull and vertebral column, respectively)
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Three membranes of meninges
1. Dura matter 2. Arachnoid membrane 3. Pia mater
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Cerebrospinal fluid
Fills sub-arachnoid space covering brain and spinal cord, similar to blood but with few proteins and RBC or WBC, produced by choroid plexus in ventricles, supports the CNS and provides cushioning against injury
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Blood supplies from three main arteries
1. Anterior 2. Middle 3. Posterior cerebral arteries
Receives input from vertebral and internal carotid arteries
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Spinal cord is supplied by three main arteries
1. Anterior spinal artery 2. Right 3. Left posterior arteries
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Barriers in blood supply
Tightly packed endothelial cells, help maintain environment of CNS
Impedes passage of: foreign substances, proteins/other large molecules, highly charged molecules, hormones and neurotransmitters
Glucose actively transported
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Why is the barrier in blood supply weak in some areas?
Allows monitoring of chemical composition of blood
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Somatic (PNS)
Conscious, provides sensory and motor innervation, sensations such as light and pain, voluntary movements
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Autonomic (PNS)
Unconscious, regulates organ functions that maintain homeostasis, has 2 efferent components: sympathetic & parasympathetic
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Second stage neurons in autonomic
Far from target in sympathetic, but near target organ in parasympathetic
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Cranial Nerves Acronym
On Occasion Our Trusty Truck Acts Funny, Very Good Vehicle Any How
Some Say Marry Money, But My Brother Says Big Brains Matter Most
(S-sensory, M-motor, B-both)
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Major divisions of the brain (5)
Forebrain: 1. Telencephalon (cerebrum) 2. Diencephalon
Midbrain: 3. Mesencephalon
Hindbrain: 4. Metencephalon 5. Myelencephalon
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Layers of neocortex (6)
1. Axons and dendrites, synaptic integration 2. Densely packed stellate cells and a few pyramidal (input/output to other areas) 3. Loosely packed stellate cells with intermediate sizes pyramidal cells (input/output) 4. Bands of densely packed stellate cells, no pyramidal (input from thalamus) 5. Very large pyramidal cells, few loosely packed stellate (output brainstem/spinal cord) 6. Pyramidal cells of various sizes, loosely packed stellate (output to thalamus)
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Pyramidal cells
Output neurons, excitatory
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What causes columnar organization?
Vertical axons and dendrites, parallel processing
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Stellate cells
Local circuit, both excitatory and inhibitory
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Korbinian Brodmann
Defined ~50 distinct regions of neocortex, different structures=different functions
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Neocortex has 3 parts
1. Sensory 2. Motor 3. Association (higher-order)
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Brodmann areas and functions
MEMORIZE DIAGRAM ON SLIDE
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Fiber tracts in white matter (3)
1. Association- connect gyri in same hemisphere (short and long) 2. Commissural- connect corresponding gyri in opposite hemispheres
3. Projection- connect cerebrum with other parts of brain and spinal cord
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Subcortical areas (3)
1. Basal forebrain 2. Basal ganglia 3. Limbic system
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Basal forebrain
Includes nucleus accumbens (motivation and rewards) and nucleus basalis (sleep-wake cycle and learning and memory)
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Basal ganglia
Includes caudate & putamen (striatum), gloves pallidus, subthalamus (diencephalon), and substantia nigra (mesencephalon)
Plays a role in selection of which of several motor actions to execute at any given time. Damage=Parkinson's or Huntington's
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Limbic system components (3) and overall function
1. Cerebral cortex 2. Subcortical 3. Diencephalon
Basic motivations (hypothalamus), emotion (amygdala), and learning and memory (hippocampus)
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Cerebral cortex of limbic system
Made up of hippocampus and cingulate cortex
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Subcortical of limbic system
Made up of amygdala and septum
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Diencephalon of limbic system
Made up of hypothalamus, mammillary bodies, and anterior nuclei of thalamus
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Spinal cord white matter
Organized into various ascending (somatosensory) and descending (motor) tracts
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What is the thalamus separated by?
Lamellae (fibers; white areas)
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Functions of the thalamus (3)
1. Process/relay somatic nervous system info to cerebral cortex
2. Sleep/wake states
3. Consciousness
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Ascending sensory inputs (5)
1. Medial geniculate body-sends to auditory primary cortex
2. Lateral geniculate body-sends to visual cortex
3. VPN- projects to post central gyrus, processes touch
4. Ventral lateral nucleus- input from cerebellum, do it well
5. Ventral anterior nucleus- input from basal ganglia
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Functions of hypothalamus (3)
Primitive functions
1. Motivates search for food, drink, sleep, temp, mates
2. Controls activities of autonomic nervous system
3. Links nervous system to endocrine system by synthesizing and secreting hormones
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Tectum
Roof, dorsal surface
Composed of superior and inferior colliculi
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Tegmentum (3 colorful nuclei and 2 tracts)
Aka cerebral peduncles
Colorful nuclei:
1. Periaqueductal grey (cell bodies)
2. Red nucleus
3. Substantia nigra
Two major fiber tracts:
1. Medial lemniscus
2. Pyramidal tract
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Periaqueductal gray (cell bodies)
Pain modulation and defensive behavior
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Red nucleus (iron)
Motor coordination
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Substantia nigra (melanin)
Movement selection (part of basal ganglia)
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Medial lemniscus
Somatosensory fibers ascending to VPN of thalamus
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Pyramidal tract
Motor axons from primary motor cortex descending towards spinal cord
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Metencephalon
Pons and cerebellum
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Pons
Divided into dorsal and ventral pons
Dorsal: nuclei for 4 cranial nerves, sensory and motor functions
Ventral: pontine nuclei, receiving input from descending fibers of pyramidal tract, nuclei project axons into cerebellum via middle cerebellar peduncle
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Metencephalon
Cerebellum, connected to brain stem by cerebellar peduncles
- Superior: primary output (VL thalamus; red nucleus)
- Middle: input from contralateral motor cortex via pontine nuclei
- Inferior: input from ipsilateral inferior olive
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Myelencephalon
Medulla oblongata, oldest portion of the brain
Ventral medulla surrounds central canal, dorsal medial is anterior to 4th ventricle
Connects higher levels of the brain to the spinal cord, regulates basic functions
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Medulla
Regulates basic autonomic functions
Contains dorsal column nuclei (cuneatus and gracilis; touch), solitary nucleus (taste), cochlear nucleus and ventral part of superior olive (hearing), inferior olivary nucleus (motor coordination)
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2 major fibers tracts in myelencephalon
1. Medial lemniscus: ascending somatosensory fibers in dorsal column nuclei, axons cross brain stem and ascend to thalamus
2. Medullary pyramids: descending motor axons from primary motor cortex
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Reticular Formation
Not a single structure, complex network of ~100 tiny nuclei that span the lower brainstem
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Functions of reticular formation
Sleep wake transitions, arousal/attention (reticular activating system), voluntary motor control, reward and addiction (ventral tegmental area), and mood (locus coeruleus, Raphe nuclei)
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Genetic and environmental causes of nervous system disorders (2)
1. Gene copy number variation
| 2. Mutations in genes or regulation regions
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Phases of Development
1. Ovum + sperm = zygote (cell division)
2. Neurogenesis
3. Structure formation
4. Wiring the brain
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Germinal Stage
Potency:
- Totipotent: fertilized egg--> morula
- Pluripotent (embryonic stem cells): blastocyst
- Multipotent; unipotent
End of stage: "baby in a compact disc"
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Gastrulation
Migration of blastocyst cells inward, leading to multiple distinct layers of tissue called germ layers
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Neurulation
```
Nervous system emerges
Stages:
-Neural tube: CNS
-Inside tube: ventricles and spinal canal
-Neural crest: PNS
-Somite: skull and vertebrae
```
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Induction
When cells and tissues interact with one another to orchestrate developmental processes
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Mangold and Spemann (1924)
Embryonic induction, transplanted dorsal lip (future mesoderm, called the organizer) of one frog blastopore induced a second neural tube in a recipient frog embryo
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What causes induction of the neural plate?
Blockage of an inhibitory signal within ectoderm (process called disinhibition)
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How do cells become neurons?
When they dissociate, separated by removal of calcium from the medium
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Bone morphogenetic protein (BMP)
If added to dissociated culture dish, then cells develop into epidermis again. BMP inhibits (prevents) a neural fate
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What molecules interfere with BMP signals?
Released by dorsal lip in amphibians, blocks anti-neural effects of BMP, induces region of embryo to develop into neural tissue=brain and spinal cord
- Ceberus (Cb)
- Chordin (Chd)
- Noggin (Nd)
- Follistatin
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Neural Tube
Forms 2 plates
1. Dorsal aspect of tube develops into roof plate in response to BMP being released by non-neural ectoderm. Releases BMP and Wnt
2. Ventral part of tube turns into floor plate in response to release of SHH from notochord. Secretes SHH
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Is BMP sensory or motor?
Sensory (dorsal)
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Is SHH sensory or motor?
Motor (ventral)
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What does symmetrical cell division (cell proliferation) result in?
More radial glial cells
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What is neural still cell proliferation (symmetric cell division) and differentiation (asymmetric cell division) controlled by? (2)
1. Morphogenetic factors
| 2. Cell-to-cell signaling
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Morphogens
Soluble molecules that diffuse and control cell fate decisions in a concentration-dependent fashion
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What does Notch do?
Suppresses differentiation in other cells (lateral inhibition)
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Lateral expansion
Symmetric, proliferation divisions, bigger
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Radial growth
Asymmetric, neuro genetic and differentiative divisions, thicker
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Gross Morphology
Proliferation and differentiation cause the neural tube to change its size and shape
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Where are shape changes (morphology) most pronounced?
Rostral end of tube (future brain and cerebellum)
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Temporal order of what the rostral end of the tube shows
1. Three swellings which give rise to the forebrain, midbrain, and hindbrain
2. Five dwellings which give rise to major divisions of the brain
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Milestones in morphological development of forebrain (4)
1. Flexion forwards
2. Posterior growth of telencephalic swellings so that they lie over, lateral to and fuse with diencephalon
3. Sprouting from diencephalon of optic stalks and cups that give rise to optic nerves and retinas
4. Sprouting from ventral surface of cerebral hemispheres of olfactory bulbs
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Milestones in the morphological development of midbrain (3)
1. Dorsal surface (tectum) shows four bumps (colliculi)
2. Floor of midbrain becomes tegmentum and projection fibers accumulate on lateral edges
3. Cerebral aqueduct narrows
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Milestones in hindbrain (2)
1. In metencephalon, tissue along dorsal-lateral wall grows to form rhombic lips and expands to form cerebellum
2. In myelencephalon, ventral and lateral walls swell so 4th ventricle is at the roof and projection fibers pass along the ventral surface
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Where can neurogenesis be seen?
Olfactory bulb and hippocampus
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What two things govern migration of cells?
Time and location
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Migrating cells
Immature (lacks dendrites and axons)
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What are two major ways for a cell to migrate?
1. Radial 2. Tangential
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Functions of radial glial cells (2)
1. Progenitors to produce (by asymmetric cell division) neurons and glia 2. Migratory guides for the newly generated neurons
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Migration patterns (Spinal cord, PNS, brain)
Spinal cord: radial
PNS: tangential
Brain: radial (67%), tangential (33%)
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Corticogenesis
Formation of cortex (6 layers), preplate is created first which separates into marginal zone
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Protein Reelin
Released by Cajal-Retzius cells in marginal zone, allows newly arrived cells to pass through existing plates since cortex is assembled “inside-out”
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Neuro-progenitor cells (NPCs)
Initially express high levels of pro-neural genes. Later the level drops and NPCs become gliogenic
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What do gliogenic cells differentiate into?
First into astrocytes and then later into oligodendrocytes as Notch signaling decreases from high to low
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Which connections in the cortex are the most dense?
Connections “up” and “down” within thickness of cortex vs connections that spread side to side
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Protein semaphorin 3A
Secreted by cells in marginal zone, attracts dendrites and repels axons
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Cell fate decisions in spinal cord controlled by 3 morphogens
1 and 2. Release of BMP and Wnt from roof plate causes dorsally located neural precursor cells to develop into sensory neurons 3. Release of SHH from the floor plate induces ventrally located precursor cells to become motor neurons
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PNS development
Develops from neural crest cells; migration of precursor stem cells is tangential in nature
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What are cell fate decisions in PNS controlled by?
Complex spatiotemporal patterns of gene expression
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Aids to aggregation (3)
1. Cell Adhesion Molecules (CAMs)
2. Gap junctions pass cytoplasm between cells
3. Morphogenic factors
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Cells in commissural plate
Cells release morphogens fibroblast growth factor (Fgf8) which affects expression level of transcription factors Pax6 and Emx2. Fgf8 (and Pax6) promotes development of anterior structures. Emx2 promotes development of posterior structures
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What happens if mice are engineered to produce less Emx2?
Expansion of anterior cortical areas such as motor cortex and shrinkage of posterior cortical area such as visual cortex
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What happens if Pax6 is knocked out?
Expansion of visual cortex (posterior) and shrinkage of motor cortex (anterior cortical area)
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Growth cone
Growing tip of a neurite. Has thin spikes called filopodia that extend and retract to probe the environment
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Chemoaffinity hypothesis
Neurons make connections with their targets based on interactions with specific molecular markers=follows guidance cues (ex: cutting optic nerve in frog)
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Multi step process of pathway formation (for axons-3)
1. Pathway selection (to a structure)
2. Target selection (to a sub-structure)
3. Address selection (particular zone)
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Pathway formation depends critically on communication between cells (3)
1. Long-range
2. Short-range
3. Neural
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Chemorepulsion/ contact repulsion
Long range: Semaphorins
Short range: Eph ligands, ECM (ex: tenascins)
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Chemoattraction/ contact attraction
Long range: Netrins
Short range: Ig CAMS, Cadherins, ECM (ex: laminins)
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Chemical guidance cues
Attract or repels, long-range or short-range
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Long range cues
Axons grow in dot to dot manner, once Netrin is high —> switch —> slit produced and repulses (Robo is a slit receptor)
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Short range cues result from two types of contact
1. Direct cell to cell contact
| 2. Contact between cells and extra cellular secretions
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Ephrin signaling
Axons expressing the receptor eph are repelled by their contact with cellular membranes expressing ephrin
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Short range ECM
Secreted to provide structural support to tissue, axon elongation occurs if integrins on their surface bind to laminin proteins in ECM, travel is aided by fasciculation
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Synapse Formation
Process enhanced by presence of glial cells (especially astrocytes)
1. Axon releases agrin
2. Agrin binds to MuSK on muscle cell membrane
3. MuSK activates rapsyn, promotes migration of postsynaptic acetylcholine receptors to synapse
4. Muscle cell releases calcium, induces cytoskeletal changes in axon to assume morphology of terminal bouton
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Synapse Rearrangement
Diffuse pattern of synaptic contact is characteristic of early development, more focused pattern is present after synaptic rearrangement
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Synapse rearrangement- two mechanisms
1. Apoptosis
| 2. Neural activity
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Apoptosis
Triggered if a neuron fails to obtain life preserving chemicals (ex: neurotrophins) supplied by its targets
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Hebbian modification
If one neuron is important to another, increases efficacy when pre synaptic and post synaptic neurons are coactive
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Growth is a consequence of (3)
1. Synaptogenesis
2. Myelination
3. Dendritic branching
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Many opportunities for experience to influence development (3)
1. Deprivation vs enrichment
2. Critical period
3. Sensitive period
