the hippocampus1Neuronal Cell BiologyLectures 1 & 3 Michael NonetLecture 2 Kelly MonkMichael Nonet958 McDonnell747-1176 [email protected] all of these have Nervous systems?3Ramon y Cajal (1852 –1934)Cajal’s drawing ofcerebellar Purkinje cellsSpanish histologist, physician, pathologist and Nobel laureateThe most famous pioneer in the descriptive anatomy of nerve cells4Brainbow hippocampus5without color6Ramón y Cajal introduced the four principles which comprise the neuron doctrine Cellularity: "The nerve cell is the fundamental structural and ! functional element of the brain."Synaptic communication: "The terminals of one neuron's axon communicate! with the dendrites of another neuron only at specialized sites, ! later named synapses by Sherrington."Connection specificity: "Neurons do not form connections indiscriminately. ! Rather each nerve cell forms synapses and communicates with certain ! nerve cells and not with others."Dynamic polarization: "Signals in a neural circuit travel in only one direction. . . ! Information flows, from the dendrites of! a given nerve cell to the ! cell body, then along the axon to the presynaptic terminals and then ! across the synaptic cleft to the dendrites of the next cell, and so on.”Neuron Doctrine7What is our goal as neuroscientists Understand how neurons: - are organized into a cohesive organ - develop into a mature organ - function individually and in units - respond to injury - becomes dysfunctional in disease8Outline of lectures• LECTURE 1 INTRODUCTION TO NEURONS• Organizational principles of nervous systems• Overview of cell biology of a typical cell and a neuron emphasizing differences• Signaling in Neurons - Transmitters• LECTURE 2 GLIA (Kelly Monk)• LECTURE 3 HANDLING DISTANCE IN NEURONS• Axonal transport• Local translation and local degradation9Preparations and Techniques in Neuroscience• Often multiple ways to answer the same question– In vivo vs. In vitro; physiological vs. behavioral, etc.• Many different experimental preparations available– Cultured cells, dissected preps, whole behaving animals– Different preps have distinct strengths and weaknesses • Many different techniques to use– Learn how they work (so you can tweak them)– Learn their strengths, weaknesses and limitations (so you use them appropriately)10Composition of neuronal tissue• Neurons– Receive and transmit information– Both excitatory and inhibitory types• Glia – Myelinate axons– Act as support cells (uptake of transmitter) – Regulate aspects of brain development and function • Vasculature (in larger organisms)– Delivery nutrients oxygen, remove waste11Diversity of nervous systemsAnimalNeuronsGliaSynapsesnematode302 - 38356~7,000apylsia~18,000yes; number?likely >1 millionfruit fly~100,000yes; number? likely >10 millionmouse~75 million~23 million~100 billionhuman86 ± 8 billion84 ± 10 billion~100 trillionAre there any common principles about how these are organized?White et al. 1986; Cash and Carew 1989; Chiang et al 2011;Williams 2000; Azevedo et al. 200912Organization of nervous tissueSensory inputMotoroutput Central Processing13A typical neuronSoma•Site of most protein synthesis•Axon hillock-site of axon potential initiation Axons•Often myelinated •Thin uniform caliper (<10 um , typically 1 um diameter)•Neurons usually have only one though it often branches in target area•Site of nerve terminals: presynaptic specialization for releasing transmitterDendrites• Thick and tapered• Rarely myelinated • Often many dendrites • Multiple levels of branching• Inputs often on dendritic spines• Integrate small conductances (from many synaptic inputs)14Dendritic, somatic, and axonal compartments specialized in different neuronal types - specialized dendritic compartments in sensory neurons - specialized axons in relay interneurons- enlarged synapses in motor neuronsSome examples:15Sensory neurons very diverse• Touch - Mechanosensory neurons• Smell - Olfactory neurons• Taste- Gustatory cells• Vision- Rods and cones• Sound- Hair cells • Nociception- heat, cold, pain,16Diverse sensory neurons17Mauthner cells in fish- A pair of reticulospinal neurons involved in quick escape reflexes-very large diameter axon (0.1 mm in goldfish)-mixed chemical and electrical synapseshttp://www.nbb.cornell.edu/neurobio/Fetcho Liu & Fetcho 1999 Neuron 23:325 – 335.Korn & Faber 2005 Neuron 47:13-28.18Specialization of synaptic outputsThree type of cell-cell signaling -electrical synapses -chemical synapses -diffuse modulatory release19Synaptic contacts• Electrical synapses– Direct electrical connections between cells– Fast with little temporally delay– Composed of gap junctions • homo or heteromeric assembles of connexins or innexins which are• hexameric transmembrane complexes that form channels. –Can be rectified Neuroscience, 4th edition fig 5.220Gap junctions roles• Required for function of circuits– Reflex circuits (escape responses in flies and fish)– Signal averaging in retina (cone, rod and amacrine cell coupling) • Required for development of circuits– Left-right asymmetry of neuronal pairs in worms (Chuang, 2007)– Synapse formation in leech (eg. Todd et al. 2010)– Calcium wave propagation in retina (eg. Wong et al 2 • Critical in Schwann cell function– Cx32 lesions lead to Charcot-Marie-Tooth-disease 1X21Ca2+ waves in developing RGC in retinaMovie: Wong et al. 199822Cx32 localization in Schwann cellsKleopa, K A J. Neurosci. 2011;31:17753-1776023Synaptic contacts synapse structure varies tremendouslyNeuroscience, 5th edition fig 5.3• Chemical synapses-Chemical signaling-Depolarization drives Ca influx-Transmitter filled vesicles fuse-Transmitter diffuses across cleft and activates postsynaptic receptor-Effect on postsynaptic cell determined by transmitter and receptor activated-Signaling event terminated by degradation or uptake of transmitter-2-3 ms delay between presynaptic and postsynaptic response 24A typical CNS synapse 0.3 µmImages:Cajal 1899 Burns and Augustine 1985 ;Atlas of Ultrastructural Neurocytology1.6.13;- small and numerous- a low probability of release- plastic both structurally and functionally- release has a small effect on membrane potential- post synaptic cell integrates multiple inputs to fire25-huge pool of vesicles -100 docked SVs and 800 tethered SVs-ongoing SV fusion, rate regulated by calcium-ribbon: