Neurotransmitters can be made in both the soma or in the axon terminal Reuptake Pumps recapture release neurotransmitters for

r reuse (very rapid response) Types of Neurotransmitters - Amino Acids: Glutamate (excitatory); GABA (inhibitory) - Biogenic Amines: Acetylcholine - Biogenic monoamines: dopamine, norepinephrine, epinephrine, tyramine, serotonin, histamine - Purines: Adenosine, ATP and derivatives (ex: caffeine) - Small Molecules: Carbon Monoxide, Nitric Oxide, Zinc - Fatty Acids: Anandamide Plaques abnormal cluster of protein fragments between cells Tangles twisted strands of protein inside dead and dying nerve cells interfere with transport systems interfere with cell function Neurodevelopment - Majority of neurodevelopment and neurogenesis occurs before birth - Dendrites and Axons continue to grow throughout life - Undeveloped neurons may occur due to disease or a lack of neuronal/environmental signals - Neurogenesis many cells initially selection migration differentiate - Competitive Elimination occurs after birth to select the most fit neurons *In some disorders, defective neurons are selected and cause disease when neurons are called on Adult Neurogenesis Neurogenesis continues in adulthood only in the hippocampus and olfactory bulb - Negative Factors: Stress, Depressing, Aging, Neurodegeneration - Promoting Factors: Exercise, Learning, Neurotrophic Growth Factors, Anti-Depressants - Neurotrophic Factors: - NGF, P75, TrkA, GDNF, EGF, FGF, ILGF, CNTF, etc. - Brain Derived Neurotrophic Factor (BDNF) *Modulation of neurotrophic factors can alter development and maintenance of neurons Functional Synapse - Energy provided by mitochondria - Chemical transmitters stored in vesicles - Receptors are located on both sides of the synaptic cleft - Many neurons utilize more than one neurotransmitter at a single synapse - neurons release only one or both in varying amounts depending on the need - By Age 6, most synapses are present - over next 5-10 years, half of the connections are removed (pruning) - over-pruning can cause a loss of inhibitory neurons over-excitation Glial Cells - Play supporting role structural, scavenger, buffer K+ ion concentration - can also differentiate into neurons or Astrocytes - contain a form of excitability based upon Ca2+-signaling - Line blood-brain-barrier - Astrocytes may even play a communicating role with neurons Neurotransmission - communication within a neuron is electrical - communication between neurons is chemical - Post-Synaptic Neurons are talk back to the Pre-Synaptic Neurons

- ex: Loop Circuits, Retrograde Communication Damages to the Communication of Neurons -Initially: Loss of an inhibitory neuron over-excitation of cells severe motor disorder - Later: Relief of over-excitation by reducing signally (down-regulation) mild motor disorder decrease in symptoms over time ***Most powerful way of a neuron to change its function is to alter gene expression - ex: up-regulation and down-regulation Signal Transduction Binding of 1st messenger activation of ion channel formation of 2nd messenger rd th activation of 3 and 4 messenger activation of early genes activation of late genes long-term effects of late gene products - ex: G-protein (Metabotropic) 1st messenger: neurotransmitter 2nd messenger: cAMP 3rd messenger: Protein Kinase A 4th messenger (gene expression): CREB - ex: Ion-Channel (ionotropic) 1st messenger: neurotransmitter release Ca2+ nd 2 messenger: none 3rd messenger: CaMK (Calmodulin-dependent Protein Kinase) 4th messenger (gene expression): CREB Partial Agonists - function depends upon conditions before the partial agonist is introduced - Partial Agonist w/Full Agonist = antagonism - Partial Agonist w/none = agonist Example: Dopamine - Metabotropic Receptors D1 receptor increase cAMP D2 receptor decrease cAMP (suppress Ca2+ currents + activate K+ channels) - Function: motor planning and execution, reward process, cognition, attention, working memory, motivation, mood, emotions, sleep, prolactin production - Treatment - Parkinson dopamine agonist - Antipsychotic/Anti-maniac D2 Antagonist and Partial Agonist - ADHD Dopamine Reuptake Inhibition - Drug Abuse Release Dopamine - Depression reduction in dopamine metabolism Example: Serotonin - Metabotropic Receptor 5-HT1 adenyl cyclase, K+, Ca2+ conductance 5-HT2 G proteins and Phospholipase C - Ligand-Gated Receptor 5HT3 lead to emesis

involved in temp. regulation, mood, anxiety

Example: Acetylcholine - Metabotropic Receptor M1, M2, M3, M4, M5 influx of Na+ K+, cAMP, IP3/DAG pathway - Ligand-Gated Ion Channel Nicotine Receptor

increased cation conductance