9.14 - brain structure and its origins spring 2005 ...€¦ · a sketch of the central nervous...
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A sketch of the central nervous system and its origins
G. Schneider 2005
Part 1: Introduction
MIT 9.14 Class 2Neuroanatomical techniques
9.14 - Brain Structure and its OriginsSpring 2005Massachusetts Institute of TechnologyInstructor: Professor Gerald Schneider
Primitive cellular mechanismspresent in one-celled organisms and retained in the evolution of neurons
• Irritability and conduction• Specializations of membrane for irritability• Movement • Secretion• Parallel channels of information flow; integrative
activity• Endogenous activity
The need for integrative action in multi cellular organisms
• Problems that increase with greater size and complexity of the organism:– How does one end influence the other end?– How does one side coordinate with the other side?– With multiple inputs and multiple outputs, how can
conflicts be avoided (often, if not always!)?
• Hence, the evolution of interconnections among multiple subsystems of the nervous system.
How can such connections be studied?
• The methods of neuroanatomy (neuromorphology): Obtaining data for making sense of this “lump of porridge”.
• We can make much more sense of it when we use multiple methods to study the same brain. E.g., in addition we can use:– Neurophysiology: electrical stimulation and recording– Neurochemistry; neuropharmacology– Behavioral studies in conjunction with brain studies
• In recent years, various imaging methods have also been used, with the advantage of being able to study the brains of humans, cetaceans and other animals without cutting them up. However, these methods are very limited for the study of pathways and connections in the CNS.
A look at neuroanatomical methods
Sectioning
Figure by MIT OCW.
Cytoarchitecture:Using dyes to bind selectively in the tissue --
Example of stains for cell bodies
Ventromedialnucleus ofhypothalamus(VMH)
Rat brain,Coronal sectionNissl stain(cell bodies)
Specimen slide removed due to copyright reasons.
Fiber architectureExample: visualizing a chemical that binds to myelin
Myelo-architecture of human midbrain
Figure removed due to copyright reasons.
Chemoarchitecture, example:Acetylcholinesterase stain: Layers and patches in
rat midbrain
Specimen slide removed due to copyright reasons.
More chemoarchitecture: DorsalVentricularRidge
Striatum
PIGEON TELENCEPHALON
Neocortex
Striatum
SQUIRREL MONKEY TELENCEPHA
Histochemistry applied to comparative neuroanatomy of the forebrain
See Nauta & Feirtag, p.30, for another example
Figure by MIT OCW.
Sketches of photos of acetylcholinesterase-stained sections of telencephelon of pigeon (above) and squirrel monkey (below).
Immuno-histochemistry,
example:
Opiate receptor localization in
rat brain
Golgi Stain:
Used by Ramon y Cajal to study connectivity
of the brain and spinal cord
(Courtesy of Nathaniel McMullen. Used with permission.)
Santiago Ramon y Cajal, drawing at his
microscope
Golgi Method: axons in spinal cord (Ramon y Cajal)
Figure removed due to copyright reasons.
Please see:Cajal, S., and Ramón Y. Histology of the Nervous System of Man and Vertebrates.
Translated from the French by Neely Swanson, and Larry W. Swanson. 2 vols.
New York, NY: Oxford University Press, 1995. ISBN: 0195074017.
Ramon y Cajal: Neurons of spinal cord
Figure removed due to copyright reasons.
Please see:Cajal, S., and Ramón Y. Histology of the Nervous System of Man and Vertebrates.
Translated from the French by Neely Swanson, and Larry W. Swanson. 2 vols.
New York, NY: Oxford University Press, 1995. ISBN: 0195074017.
Ramon y Cajal: Diagram of local reflexes
Cajal saw an entire S-Rpathway for the first time.
Figure removed due to copyright reasons.Please see:Cajal, S., and Ramón Y. Histology of the Nervous System of Man and Vertebrates.Translated from the French by Neely Swanson, and Larry W. Swanson. 2 vols.New York, NY: Oxford University Press, 1995. ISBN: 0195074017.
Brain connections and behavior• The story of Karl Lashley’s encounter, as a
young student, with slides of a frog brain. “If I could use this kind of material to see all of the connections, it would be possible to explain the frog’s behavior.”
• Assumption: the S-R model originating with RenéDescartes, championed by LaMettrie in the following century, boosted by the Russians Sechenov and Pavlov.
• Later, Lashley argued against the adequacy of S-R theory for explaining temporal order in rapid sequences of behavior…
• Return to the primitive cellular mechanisms: the role of endogenous activity. (More about that later.)
• Motivational systems can initiate behavior, using inputs as guides.
• Nevertheless, the S-R model remains a common assumption among neuroscientists.
Connectivities: How do we know about them?
• Dissection• Staining techniques: cells, fibers; uniqueness of Golgi methods• Complexity problem: How to be sure of a connection?
– Historical example: How does info get from eye to neocortex?• Electrophysiology: Sherrington et seq.; “antidromic” stimulation and
recording• Marchi method: an experimental anatomical technique.• Nauta methods for silver staining of degenerating axons.• Labeled amino acids and autoradiography• HRP histochemistry: 2-way transport utilized• Fluorescent tracers• Immunohistochemistry: chemoarchitecture; new tracers, e.g. CT-B.
Walle J. H. Nauta1916-1994
• From the Netherlands, then came to USA viaSwitzerland
• Father of modern experimental neuroanatomy• M.I.T. Professor, 1964-1986 (Institute Professor
from 1973)• First neuroanatomist to be appointed to the faculty
of a psychology department (1964, MIT). This move by Hans-Lukas Teuber presaged the development of modern neuroscience.
Walle J. H. Nauta, M.D., Ph.D.
Walle NautaM.I.T.
Institute Professor
Photograph removed due to copyright reasons.
Example:Hamster with unilateral lesion of midbrain surface on first
postnatal day: tracing of retinal projections from left eye, using a modified Nauta silver-stain for degenerating axons
Photomicrograph(s) removed due to copyright reasons.
HRP staining, after anterograde transport from retina of hamster pup: labeled axons seen in diencephalon using dark-field microscopy
Photomicrograph(s) removed due to copyright reasons.
Bright field
Immunohistchemicalstaining for Cholera Toxin, subunit B(anterograde transport from part of retina to lateral geniculate nucleus)
Dark field
Photomicrograph(s) removed due to copyright reasons.
Retrograde tracer: Fluorogold (transport from SC to retina, seen in whole mount)
Photomicrograph(s) removed due to copyright reasons.
Double Labeling: Nuclear Yellow and HRP (retrograde transport from optic tract to retina, seen in
retinal whole mount)
Photomicrograph(s) removed due to copyright reasons.
Co-localization: fluorogold & fluorescent beads
Primitive cellular mechanismspresent in one-celled organisms and retained in the evolution of neurons
• Irritability and conduction • Specializations of membrane for irritability • Movement • Secretion• Parallel channels of information flow; integrative
activity– The need for neuroanatomical and other methods of
research• Endogenous activity
Endogenous activity: The primitive cellular mechanism often neglected
• Reasons for oversight: – Forgetting about evolution– The simplicity of the reflex model– The discomfort of dealing with actions where
the causes are not known. (Only with modern cell biological approaches are endogenous activities beginning to be understood.)
• Examples from neurons• Example of hydra behavior
Example of endogenous activity in CNS (Spontaneous CNS activity)
• Endogenously generated rhythmic potentials in neuronal membranes can cause bursting patterns of action potentials– Felix Strumwasser’s Aplysia (sea slug) recordings
(1960s, early ’70s)– There are many electrophysiological and molecular
studies of endogenous activity in neurons since the early work.
• The biological clock: Control of circadian rhythms in vertebrates
Endogenous oscillator
Felix Strumwasser’s Aplysia (sea slug) experiments
• Recordings form an identifiable large secretoryneuron of the abdominal ganglion:– T=40 sec (rhythm persists if action potentials are
blocked with TTX),– but not if sodium pump is blocked with Ouabain.
• This cell also showed a circadian rhythm that could be entrained by light.
Circadian rhythms in vertebrates
• Dependence on such “biological clocks” with a period of approximately 24 hr.
• Give mice heavy water, D2O, and their free-running circadian activity rhythm slows down to a degree proportional to the % D2O in their drinking water.
Selected References
Slide 10: Slide 6: Figure by MIT OCW. © MIT 2006. Based on: Striedter, Georg F. Principles of Brain Evolution. Sunderland, MA: Sinauer Associates, 2005, p.34. ISBN: 0878938206 Slide 6: Figure by MIT OCW. © MIT 2006 Slide 13: Self Portrait of S. Ramon y Cajal, 1920. Slide 21: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 22: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 23: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 24: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 25: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 26: Image by Gerald Schnieder. © G.E. Schneider 2006 Slide 30: Drawing by Gerald Schnieder. © G.E. Schneider 2006