1. Introduction to Neurobiology
   1. Nervous systems- a specialization unique to multicellular animals
      
   2. Comparison of neuronal vs. hormonal transmission: Fast and specific vs. slow and general.
   3. Largest concentration of neurons in vertebrates = brain
      1. 1. Brain size, infoldings reflects complexity of nervous function in animal; all neuronal cell bodies are in the outermost 0.5 mm of brain, and are nourished by the CSF; therefore, infoldings, by increasing surface area, increase cell bodies.
      2. Layered structure of brain: Go from caudal (spinal cord, hindbrain) to rostral (forebrain) - order of appearance in development and in evolution.
2. Gross Anatomy of the Nervous System
   1. Rostral vs. Caudal
   2. Dorsal vs. Ventral
   3. Medial vs. Lateral
   4. Overall Plan of the Nervous System
      1. Central Nervous System: Brain and Spinal Cord. Bathed in cerebrospinal fluid and separated from bloodstream by blood-brain barrier. Physical substrate of blood-brain barrier: vascular endothelial cells linked together by tight junctions. In CNS, axons are bundles together in fascicles or tracts.
      2. Peripheral Nervous System
         1. Cranial Nerves - Concept of a nerve:
            1. Axons Myelinated or Unmyelinated
            2. Bundled together with very small blood vessels and loose connective tissue called the endoneurium, by a denser sheath called the perineurium - to make peripheral fascicles.
            3. Fascicles are surrounded by larger blood vessels and a connective tissue called the epineurium.
         2. Spinal efferents and afferents
         3. "Autonomic" nervous system
            1. Sympathetic
            2. Parasympathetic
            3. Enteric
            4. Central control of autonomic nervous system - blood pressure regulation, heart rate, nausea and vomiting, etc. Better term would be indirect nervous system
   5. Brain Gross Anatomy
      1. Meninges
         1. Dura Mater - cartilaginous membrane
         2. Arachnoid - spongy membrane system - filled with CSF
         3. Pia Mater - thin membrane, closely adherent to brain surface.Richly invested with blood vessels.
   6. Divisions of Brain
      1. Hindbrain (Rhombencephalon). Made up of:
         1. Myecephalon (Medulla oblongata)
         2. Metencephalon (Pons & Cerebellum)
      2. Midbrain (Mesencephalon)
      3. Forebrain (Prosencephalon) Made up of:
         1. Diencephalon (Thalamus, Hypothalamus,Pineal body)
         2. Telencephalon (Cerebrum, Olefactory bulbs, Basal ganglia)
         3. Divisions of Cerebrum
            1. Lobes: frontal, temporal, parietal, occipital
            2. Fissures: deep clefts
               1. Sagital fissure - separates left & right hemispheres - spanned by corpus callosum
               2. Sylvan fissure - separates temporal, parietal lobes
            3. Infoldings = sulci; bumps = gyri
               1. Biggest sulcus = Central sulcus. Separates precentral gyrus (primary motor cortex) from postcentral gyrus (primary sensory cortex)
         4. Vertical organization of the brain
            1. Neuronal cell bodies are found at the surface of the cortex - intimate contact with CSF.
               1. Layers I - III - interneurons
               2. Layer IV Interneurons + large afferent neurons
               3. Layer V - projection neurons (pyramidal neurons): major output pathways
               4. Layers VI, VII - interneurons
            2. Inner portions of cortex - tracts of myelinated axons = white matter. Radiates from foot of the brain out to the surface = Corona Radiata
   7. Cortical Efferent (motor) pathways. (voluntary motor pathway - pyramidal tract - for now)
      1. Projection from cortex to midbrain (cerebral peduncles) through myelinated tracts of cerebral white matter = Corona Radiata. Forms cortico-spinal tract.
      2. Projection from midbrain through the pons - branching of cranial nerves (will include both efferent (motor) and afferent (sensory) functions:
         1. (I) Olfactory - sensory
         2. (II) Optic - sensory
         3. (III) Oculomotor - motor; eye muscles except lateral rectus and superior oblique.
         4. (IV) Trochlear - motor; Superior oblique muscle of eye
         5. (V) Trigeminal - mixed:
            1. Opthalmic branch - sensation from eyelid, etc.
            2. Maxillary branch - sensation from upper jaw.
            3. Mandibular branch - sensation from lower teeth and jaw; motor - muscles used in chewing.
         6. (VI) Abducens - motor - lateral rectus muscle of eye.
         7. (VII) Facial - mixed - sensation from front 2/3 of tongue; motor innervation of facial muscles.
         8. (VIII) Auditory nerve (Vestibulocochlear) - sensory - hearing and organs of balance.
         9. (IX) Glossopharangeal - mixed - sensation from back of tongue; motor innervation of muscles involved in swallowing.
         10. (X) Vagus - mixed - Motor: Autonomic fibers of the parasympathetic nervous system that innervate smooth muscles of the organs; muscles involved in speech. Sensory: Visceral sensations from gut
         11. (XI) Spinal Accessory - motor - muscles of neck and shoulders (sternomastocleid and trapezius)
         12. (XII) Hypoglossal - muscles of tongue
      3. Decussation of the pyramids - motor (and most sensory) function crosses to contralateral side of the body - just below cranial XII. Contralateral innervation above this point (i.e., in the cranial nerves) must cross in a separate structure, such as the optic chiasm.
   8. Spinal Cord
      1. Meninges of the spinal cord
      2. Spinal cord proper
         1. Gray matter (cell bodies) - central "butterfly"
         2. White matter (myelinated axonal tracts) is peripheral. The major motor tracts (pyramidal tracts) run in the ventrolateral portion, and the sensory tracts are more dorsal.
      3. Segmental organization of vertebral column : branching out of spinal motor neurons is segmental.
         1. Cervical cord - innervates neck and arms
         2. Thoracic cord - innervates chest and abdomen
         3. Lumbar cord - innervates pelvis and front of legs
         4. Sacral cord - innervates buttocks and back of legs.
         5. Premotor axons descend from the brain in the ventrolateral tracts. At the appropriate segment, they dive into the gray matter to synapse on a spinal motoneuron in the ventral horn. The axons arising from these motoneurons exits the spinal column in the ventral root and bundles with the peripheral axons from sensory neurons to form a nerve which projects to the periphery.
3. The Autonomic Nervous System - a Target of the Spinal Motoneurons
   1. Sympathetic branch
      1. Localization: a chain of ganglia running beside the vertebral column from C1 (superior cervical ganglion) to S4
      2. Postganglionic nerves innervate targets in a segmental fashion: SCG innervates head and neck; lumbar and sacral sympathetic ganglia innervate colon, bladder
      3. Function: Activate energy metabolism, prepare for flight or fight: speeds up heart rate, raises peripheral resistance to blood flow, slows digestion, mobilizes energy stores.
   2. Parasympathetic branch
      1. sources of presynaptic autonomic motoneurons:
         1. Cranial Nerves III, VII, IX, X
         2. Sacral segments S2-4 (Pelvic Nerve)
      2. Postganglionic parasympathetic nerves near or in the target tissue; preganglionic segments may be long and are generally not segmental in nature (for example, the Vagus innervates smooth muscles of the lungs, innervates the heart, innervates the gut, etc.)
      3. Function: Conserves body resources and restores homeostasis; antagonistic to sympathetic branch. Slows heart rate, decreases blood pressure, increases digestive motility.
4. Sensory (Afferent) Pathways
   1. Signals from the touch, pressure, stretch, etc. receptors synapse on the terminal field of the peripheral axon of the sensory neurons. (Note that this is a blatant exception to the rule of functional polarization.) From there they project back to the appropriate dorsal root ganglion, where the signal propagates from the peripheral to the central axon of these pseudounipolar neurons. The central axon enters the spinal column through the dorsal root and may:
      1. Synapse locally on motor neurons to form simple reflex arcs.
      2. Synapse on interneurons which synapse on motor neurons to form reflex arcs.
      3. Synapse on second order sensory neurons which cross the midline and ascend to the hindbrain.
      4. Ascend or descend a few segments and synapse on interneurons involved in flexor reflex arcs.
      5. Ascend to the hindbrain before synapsing on neurons that cross the midline.
   2. Evolutionary newer ascending pathway (conscious touch) is mainly the one that ascends to the hindbrain (in the dorsal column) before they synapse on second order neurons that cross the midline. These neurons then ascend to the thalamus of the midbrain in a bundle called the medial lemniscus, which gives this pathway the name of the lemniscal pathway.
   3. Primitive ascending pathways carry deep touch and pain and temperature sensation. They synapse immediately on entering the spine and ascend to the hindbrain, and from there the midbrain (thalamus) in the spinothalamic tract. The different routing of the conscious touch and pain, temperature pathways gives rise to some diagnostic differential blockade in some cases of partial spinal cord trauma.
   4. In the thalamus, both sensory pathways synapse on neurons which give rise to axons that project to the stellate cells in layer IV of the primary sensory cortex. The axons of these stellate cells may project to various places in the brain, including on premotor neurons, giving rise to central reflex arcs, such as the Babinski reflex.
5. Imaging the brain
   1. Dissection - traditional means of ferreting out gross connectivity. Can trace the pathway of nerves in the peripheral nervous systems (example: sciatic nerve - from the sacral cord to the back of the foot) or tracts and fascicles in the CNS.
   2. Radiological methods
      1. X-ray - limitations
      2. Tomographic Methods - Method of back projections
         1. Phantom
         2. Projection of density distribution through a phantom
         3. Summation of multiple projections
         4. X-Ray Tomography - CT scan (structure)
         5. Radio wave emission tomography (NMR tomography) - MRI scan (structure - improved resolution)
         6. Positron Emission from ¹⁸F deoxyglucose - PET scan (metabolic activity - function)
   3. Higher resolution - Cellular Methods
      1. Nissl staining - aniline dyes stain nucleic acids - ribosomal RNA Stains cell body and dendrites only. Axons have no ribosomes
      2. Golgi stain: Silver-based stain that stains 10% of all neurons. Great for structure of neurons (Santiago Ramon y Cajal) but useless for connectivity
      3. Specific stains
         1. Formaldehyde-induced fluorescence of certain neurotransmitters
         2. Immunofluorescence
      4. Connectivity
         1. Anterograde tracing methods - trace source to target
            1. Wallerian Degeneration
            2. Carbocyanine dyes - stain cell membranes
            3. Radiotracers
         2. Retrograde tracing - trace target to source --- Horseradish peroxidase.
      5. Microscopy of unstained cells - Useful for isolated cells (formation of neuronal circuits in vitro. Slice preparations.)
         1. Phase contrast microscopy
         2. Differential interference contrast microscopy
         3. Fluorescent indicators of intracellular processes
            1. pH
            2. Ca⁺⁺
            3. Other ions
            4. cyclic AMP
      6. Electron Microscopy.