Synaptic Plasticity

• Long-Term Synaptic Plasticity in Mammalian Brain:

  • LTP increases strengthens when fired within the hippocampus

  • LTD weakens strength when fired within the hippocampus and cerebellum

• Tri-synaptic Circit

  • Prefrontal pathway:

    • Granule cell (with dentate gyrus)→ mossy fiber → CA3 pyramidal neurons with Shaffer collateral axons → CA1 pyramidal neurons

• LTP in hippocampus

  • Studied in hippocampal slice preparations

    • From CA3 to CA1 pyramidal neurons, 2 Shaffer collaterals tested

    • When Pathway 1 is given a tetanic stimulus, long-term potentiation occurs by increasing the effect of the stimulus after tetanus, a heightened long-term response.

    • When Pathway 2 is given a tetanic stimulus, there is no change before and after tetanus.

  • Specificity is the single pathway being strengthened when firing happens, associativity is when the second pathway increases in strength minutely when the first pathway has a strong stimulation.

• Molecular Aspect of LTP

  • CA3 Releases Glutamate, Glu binds to AMPA first, letting Na+ into the cell, which causes a depolarization event and AMPA kicks the Mg2+ from blocking NMDA, causing Ca2+ to also enter with more Na+

  • Calcium/calmodulin-dependent Kinase II (CaMKII) in Ca1 activates more spines to form during tetanic stimulation.

  • These signaling events lead to the insertion of more AMPA receptors into the post-synaptic density, making the synapse more responsive and sensitive to Glu.

• Activation of new gene expression in LTP

  • Anisomycin causes the inhibition of protein synthesis, leading to the long-term decline of strength.

  • To keep the heightened response, kinases activate adenylyl cyclase, cAMP is produced, and activates PKA, which activated CREB to promote transcription of proteins required for the growth of new dendritic spines.

• LTD in Hippocampus

  • NMDA still signaled, but Ca2+ also activates protein phosphatase instead of kinases, which leads to the internalization of AMPA receptors, making the synapse less responsive to future Glu.

• LTD in the Cerebellum

  • Purkinje cells have increased dendrite concentration which is associated with parallel and climbing fibers.

  • Recording the responsiveness of Purkinje cells shows that if both PF and CF are stimulated together, responsiveness to PF alone is depressed.

• The molecular aspect of LTD

  • Glu from parallel fibers activates AMPA receptors, depolarizing the cell and activating mGluR, which activates PLC. PLC breaks down PIP2 into DAG and IP3. DAG directly and IP3 indirectly activate PKC. PKC phosphorylates AMPA receptors and internalization occurs.

The Eye

• The uveal tract consists of the Chodoid, ciliary muscles, ciliary processes, iris, and pupil.

• Note: photoreceptors (rods and cones) are in the back, and are anchored to the pigment epithelium

• Rods are used for scotopic (low light) vision

• Cones are used for photopic (bright light) vision

• Mesotopic is in between, both rods and cones activated

• The Dark Current

  • In the dark, photoreceptors are depolarized and with a light stimulus, they become hyperpolarized in a graded fashion (more intensity increases hyperpolarization)

    • cGMP builds up in the outer segment of rods which gate Na+/Ca2+ channels.

  • In the light, cGMP levels are decreased and the Na+/Ca2+ channels close.

• Photopigments

  • Photopigments are a protein (opsin) surrounding a light-absorbing chromophore (retinal)

    • Rhodopsin found in rods

    • Transducin is a g-protein activated by opsin during light absorption

    • Phosphodiesterase (PDE) is an enzyme activated by the Ga subunit of transducin, that breaks down cGMP.

  • Light energy converts 11-cis retinal to all-trans retinal

• Trichromacy theory is when the combination of signaling from all cones activated at a given time allows us to perceive a unique color within the visible light spectrum

• Dichromatic vision (color blindness)

  • Protanopia: absence of red cones

  • Deuteranopia: absence of green cones

• M and L opsins are much more similar to each other in sequence than other opsins

• ON-center and OFF-center RGCs help us see the contrast of vision and respond differently to varying levels of illumination in the center.

Visual Processing

• Sensory input: luminance and contrast, color, orientation/angle, and motion

  • Important for the discrimination of objects, localization of objects, movement of the eye to keep objects in focus, adjustment of pupil diameter, and regulation of circadian rhythm.

• The Pupillary Light Reflex: bright light causes ciliary muscles controlling the iris to constrict the pupil.

  • If one eye has a bright light, they both constrict, a consensual response

  • The pretectum receives input from both eyes →Edinger-Westphal nucleus on both sides, → ipsilateral ciliary ganglia, which send motor commands to the ciliary body of the iris.

• The map of the visual field is upside down and left-right reversed on the retina.

• The inferior visual field is mapped superior in the brain and vice versa.

  • A disproportional amount of cortex for macula and fovea for increased acuity.

• Meyers loop of optic radiation is bottom only

• Specific neurons are tuned to a specific angle or orientation, and specific neurons fire for specific angles.

• Organization of primary visual (striate) cortex:

  • Pyramidal neurons have multiple basal dendrites and a single branched apical dendrite that spans many layers

  • Spiny stellate neurons have many dendrites that stay within a cortical layer

  • Most LGN axons form synapses with neurons in layers 4C and 4A.

  • Ocular dominance columns are inputs from either eye.

  • Interlaminar connections are who talks to whom within the striate cortex.

  • Ascending outputs go from cortex to cortex, extrastriate

  • Descending outputs go to lower brain regions

• Lateral Geniculate Reception

  • 6 cortex layers, 6 LGN layers

  • Orientated (L, R, R, L, R, L) or vice versa

  • LGN axons make synapses primarily to layer 4 of the cortex to form ocular dominance columns.

  • Radioactive tracers are taken up by the retina and go through the entire pathway to end up in the striate cortex to be shown.

    • Shows that the mixing of the pathways is not straight lines, more like a zebra pattern.

• Types of Retinal Ganglion Cells:

  • P-type RGCs are parvocellular (small) that detect details in vision (90 percent of all RGCs)

    • End up in the 4Cbeta layer of the striate cortex

  • M-type RGCs are magnocellular (large) that detect motion in vision (5 percent of all RGCs)

    • End up in the 4Calpha layer of the striate cortex, which is also the ocular dominance column area

  • K-type RGCs are Konicellular and possibly detect color vision (5 percent of all RGCs)

    • End up in blobs of layer 2/3 of striate cortex