Contact: kdelaney@uvic.ca Course outline: http://web.uvic.ca/~kdelaney/b367 Scheduled office hours: 1:00-3:00, M&Th Cunn. 259A Contact kdelaney@uvic.ca for other times. Quiz (0.5 hrs) midterm (1.4 hrs) 35% ; one final (3 hrs) 55%; Quiz Feb. 2 Midterm Feb. 23. Detailed lecture notes will not be posted as I don t have detailed notes to post. Pertinent parts of powerpoint presentations will be posted as pdfs. Text: Neuroscience; Purves -- 5 th edition Quiz about here Midterm about her 1
Lecture 1 to 2 Generally speaking what is neuroscience and what are nervous systems? Cells in nervous tissue: - Non-neural cells in brains -- glia - Neurons: what makes them special? What is the basis for the diversity of neurons? types -- structure, ion channels, transmitters, receptors. What is a neural circuit What makes the nervous system special? ~ 6000 genes expressed only in brain Ubiquitous ~ 8000 genes expressed in all cell and tissue types Notexpressed in brain ~ 6000 genes 14,000 genes expressed in brain 2
Your brain is not like your liver vs. hepatocyte neuron Nervous systems are formed from 2 general classes of cells: neurons ( excitable ) and glia (non-excitable) 3
Patterns of gene expression for 3 calcium dependent K + channels KCa2.1 KCa2.2 KCa2.3 See also fig. 1.1 in 5 th edition Purves http://journal.frontiersin.org/article/10.3389/fphar.2012.00107/full Genetic heterogeneity at the cellular level 4
Glial (non-neuronal) cells in vertebrate brain (p8/9) Do not generate electrical activity directly but are essential elements for neural electrical functions: - unlike (most) neurons they are replaced by precursors throughout adulthood - modulate synaptic functions, - play an essential role in brain metabolism - provide a scaffold for neuronal migration during development, - maintain mature chemical homeostasis. - regulate blood flow through capillary beds - provide immune type functions Non-neuronal cells of vertebrate brains Fig 1.5 or Schwann cell D) Ependymal cells Including radial glia invertebrates have glial cells but not as many nor as specialized 5
- Ependymal cells are endothelial cells that line ventricles - In the adult brain they derive from radial glia which are present during development (see next slide) - In mature vertebrate brain some ependymal cells produce cerebrospinal fluid. Others may serve as stem or progenitor cells to make more glia and perhaps even neurons - Tanycytes (a subtype of ependymal cell) line the 3rd ventricle and extend into the hypothalamus. They are involved in transferring signals from the CSF to the CNS-- e.g. glucose levels. Probably originate embryonically from radial glial cells. 3 rd ventricle (human) Cell surface proteins act as signals to attract and motivate neurons to migrate along the surface of radial glial cells Fig. 22.12/13 5 th edition; Fig. 27.12 4 th edition 6
Myelinating glial cells: Schwann and oligodendrocyte s of motorneuron sausage roll Myelin rolled up in cross-section Oligodendrocytes are the CNS equivalent of the Schwann cells 1 schwann cell 1 motorneuron in PNS 1 oligodendrocyte multiple neurons in CNS 7
Microglia: phagocytotic cells - main elements of the intrinsic immune system - sense brain injury and clear cellular debris - derived from hemopoetic stem cells in bone marrow More and more they are implicated in brain inflammatory responses, cognitive deficits, percussive brain injury, stroke damage.. Fig. 3.20 Purves Microglia--resting and activated 8
Microglial cell expressing GFP Courtesy Dr. Sean Mulligan Blood vessel Some astrocytes retain the capacity to undergoe mitosis. 9
Astrocytes are an essential element of the blood-brain-barrier (BBB) The Blood-Brain Barrier PN01BE0.JPG CO2 2 Lac 2 Lactose glucose H2O 34 ATP glutamine O2 glutamine 2 ATP glutamate glutamate <----- 2K + 3Na + ------------> 3Na + 10
Astrocytes help to regulate blood flow to active brain regions by controlling arteriole diameter How? One clue.. changes in Ca 2+ measured in astrocytes Courtesy Sean Mulligan and Brian MacVicar Courtesy Sean Mulligan and Brian MacVicar 11
Courtesy Sean Mulligan(uSask) and Brian MacVicar (UBC) Courtesy Sean Mulligan and Brian MacVicar 12
Light absorbance 17-01-05 Every neuron is within 10-20 micrometers of a capillary in the mammalian brain Blood flow is regulated by neuronal activity through its requirement for oxygen. For intrinsic imaging experiments two kinds of light are shone on the brain surface: either green or red. Green reflectance doesn t change much with changes in oxygenation but does change with changes in total blood flow (more blood, more absorbance, less reflectance. Red reflectance is strongly influenced by the ratio of oxy to de-oxy Hb A detailed instruction manual for intrinsic imaging: www.weizmann.ac.il/brain/grinvald/pdf/neuro_research_1999_invivo_ optical_imaging.pdf 13
With lots of activity in a region of brain, O2 first drops, then the vasculature responds to bring in more oxyhb (by increasing local blood flow). On the right is the time-course of the reflectance you see with red (640 nm) illumination: B A First decreased reflectance (increased absorbance at A) due to shift from oxy to deoxyhb then more reflectance as more oxyhb is introduced (at B) since oxyhb is not a good absorber at 640 nm more light is reflected). intrinsic imaging of activity -- based on blood oxygenation whisker barrels stain presynaptic terminals changes in blood oxygenation are also the basis for functional magnetic resonance imaging (fmri) as well. 14
Intrinsic optical signal IOS.. Contralateral somatosensory cortex vibrate surface of foot Box 1A(3) or 1B Brain Imaging Techniques MRI and f(unctional)mri MRI Static. Based on water distribution fmri Dynamic B.O.L.D. based on the paramagnetic properties of Hb Poor spatial resolution but can image through skull 15
Box 1A(1) Brain Imaging Techniques CT scan Structure not activity Positron emission tomography measures metabolic activity in biochemically specific neurons e.g. dopaminergic, serotonergic using short-lived isotopes 16
Summary part 1 -- Glia are non-neural don t generate action potentials but some (astrocytes) are connected by gap junctions and act in a coordinated fashion -- 4 classes with sub-types in vertebrates. Less known about invert glia but role in creating special ionic environment around ganglia is established. -- many functions including: metabolic, immune, signaling support (myelin) and modulation (of synapses), maintain physiological homeostasis in brain 17