1. Basics:
    1. 100 billion neurons, 1000 trillion synapses, 400 cal (abt 40 W light bulb)
  2. Synapses/Synaptic Transmission
    1. history
      1. Camillo Golgi y Santiago Ramon y Cajal
        1. (Golgi) reticular theory: brain is one big network (wrong?)
          1. golgi stain w/ silver nitrate; network view
        2. (Santi y Cajal) neuron doctrine: N tissue is made of discrete cells (correct)
          1. believed there were terminals
      2. Sherrington
        1. Differences of reticular and neuron doctines: 1. flow of info is unidirectional 2. excitatory/inhibit interacts occured 3. delay in transmission of impulses b/w neurons
        2. coined "synapse"
      3. 1993: Ernst Ruska built 1st electron microscope
        1. pre/postsynaptic (cleft and vesicles) seen
    2. synapse struct.
      1. struct of chemical synapse
        1. mitochondrial magnets
        2. post synaptic density (PSD)- lots of proteins and receptors
        3. Cajal
      2. struct of electrical synapse
        1. 2 plasma membs of cells connected by gap junct's via connexin proteins
        2. Golgi
        3. Gap juncts pass elect. current from one cell to another
          1. passes current flow reflected in cell 1 to 2 -> hyper or depol (only one direction)
    3. events/elect pot
      1. Intracellular recording w/ sharp microelectrode
        1. capillary glass -> foil element covering -> heats up w/ electrical activity -> open transmission filled w/ conductor and wire-> stab it in neuron via micromanipulator -> record elect. signals
      2. Events and elect. pots at synapse
        1. Ca2+ is CRITICAL for electrical potentials
        2. communication b/w neurons: elect. -> chem.->elect.
        3. vesicles are docked and ready to fuse/release to postsynaptic membrane
      3. EPSP and IPSP in postsynaptic cells
        1. EPSP: depol/excitation of terminals uses Na+ and Ca2+
        2. IPSP: hyper/inhibition of terminals uses Cl- and K+
        3. presynaptic facilitation and inhibition
          1. synaptic integration w/ help of interneurons to facilitate + NT release
    4. NT/receptors
      1. Transmitters:
      2. Receptors:
        1. ligand gated vs G protein coupled receptor
          1. ligand: action of transmitter: 1. inactive/resting 2. active/non-desensitized 3. inactive/desensitized
          2. G-protein: bind GTP ->GDP-> diffuses and interacts w/ receptor-> charge flows or GTP-> second mgr -> ATP to cAMP -> phosphorylation and connections to receptors
          3. this is where meds bind to
      3. Mech's to Inactivate NT:
        1. enzymatic breakdown, desensitization, diffusion, uptake, oxidation, reduction
    5. Neural network: circuit interaction
      1. 1. cellular props
      2. 2. synaptic props
      3. 3. network props
      4. central pattern generator (CPG): produces patterns of activity in isolation (externally)
      5. simple reflex circuit
      6. brain funct = organization of neurons into circuits
    6. synapses
      1. Synapses and Brain Disease
      2. dendritic spines: receivers of information
      3. knowing how synapses work allows pharm. to create drugs
  3. Neuroplasticity
    1. Synaptic plasticity:
      1. hippocampal Long-Term Potentiation (LTP)
        1. spatial long term memory
        2. dentate gyrus
          1. DG -> CA3 -> CA1
        3. HM
          1. no declarative memory (names etc)
        4. glutamate receptors NMDA and AMPA in LTP
          1. causes change in DNA (transcription regulations ) -> synapse growth proteins -> store memory of synaptic input
      2. Long-term Depression (LTD)
      3. Rehab on Plasticity
        1. Intracortical Microstimulation in brain (MONKEYS)
          1. Transcranial Magnetic Stimulation (HUMANS)
        2. map of mvm't in cortex
          1. homunculus
        3. Goal directed behavior
        4. Skilled task
        5. reconfigure Motor Cortex through training
      4. Evidence Based Practice: conscientious, explicit, judicious use of current BEST EVIDENCE in making decisions about the care of the individual patient
  4. physiology at motor end plate
    1. neuromuscular junction