Self-organizing Neural Maps: The Retinotectal Map and Mechanisms of Neural Development: From Retina to Tectum

Front Matter
Copyright
Preface
Acknowledgments
Overview and basics of the retinotectal system
	Overview of the development of circuits
	Topographic maps in the CNS
	Stability, reproducibility, and flexibility
	The mature retinotectal system
	Advantages of studying the retinotectal system
	Sperry's chemoaffinity theory
	Organizational overview of the material
	References
	Further reading
Early work supports chemoaffinity with one contradictory result
	Grafted eyes regenerate optic nerves to restore vision
	Optic nerve regeneration restores original connections even when maladaptive
	Behavioral evidence of the retinotectal map and its regeneration
	Regeneration with single axis reversals
	Embryonic eye rotations and the development of polarization
	Embryonic tectal rotations with different results
	Electrophysiological mapping demonstrates regeneration of the map
		Source of the electrical signals
		Optical factors influence the map
		The retinotectal map
	Anatomical mapping of the retinotectal projection
	“Compound eyes” demonstrate the inadequacy of rigid chemoaffinity
	Qualitative models of map formation
		Rigid chemospecificity
		Distributed relative preferences
		Fiber-fiber adhesion by homophilic interactions
		Fiber-fiber sorting by activity-driven Hebbian synapses
		Contribution of pathway ordering to map formation
	Conclusion
	References
The search for chemoaffinity molecules in molecular gradients
	The monoclonal antibody approach
		The TOP antigens
		A gradient of ganglioside
		The laminin receptor
		The TRAP antigen
		Newer versions of the search for gradients and conclusions
	Culture assays of retinal fiber preferences
		Early attempts
		Stripe assays for growth cone-target selection
		Growth cone collapse as a guidance mechanism
		Response to artificial gradients
		Purification, isolation, and cloning: A tale of two factors
			RGM: The first factor
			RAGS: The second factor
		Conclusions
	The genetic approach finds a similar factor, defines the Eph receptor and ephrin ligand families
		In situ hybridization for the receptors
	Eph and ephrin family members and revised nomenclature
	The mechanism of Eph receptor control of growth cones
	Simple model of how gradients determine the RT map
	Conclusions
	References
Plasticity after surgical interventions: Size disparity experiments
	Size disparity: Compression of the projection onto a half tectum
		Implications for retinal arbors and numbers of synapses
		Compression is widespread
		Reversibility of compression
		Functional consequences of compression
	Size disparity: Half-retinal projections expand on tectum
		A model of arbor expansiveness via competition
		Implications for retinal arbors and synapses
		Maps organized without any normal chemoaffinity portion or without normal polarity
		Expansion in other species
		Evidence for a change in chemoaffinity markers in both expansion and compression
	Size disparity: Binocular projections to one tectal lobe
		Eye-specific exclusion and competition
		Models and interpretation
	Compound eyes revisited
		Tests for retinal markers in compound eyes
		Tests for tectal developmental changes
		Tests for retinal “regulation”
	Embryonic retinal ablations—Unexpected results
	Clockface model predicts compound eye from a remnant
		Cell migration following retinal lesions
		Embryonic retinal lesions in chick
		Retinal lesions in mammals
		Genetic manipulation of ganglion cell numbers in mice
	Theoretical models
		First models
		Arrow model—Polarity without positional markers
		A model without any markers
		A model with retinal induction of tectal markers
		Chemoaffinity as a weak force
		Summary of models
	Summary
	References
	Further reading
Growth of the retina and tectum: Implications for the retinotectal map
	Early morphogenesis of retina and tectum
	Histogenesis of retina
		Radiolabeled thymidine technique
	Visual consequences of continued retinal growth
		Altered magnification of the image on the retina
		Shifted location of the receptive field of each ganglion cell
		Change from aquatic to aerial vision
		Change of visual behavior with maturity
	Histogenesis of tectum—Cells added on one end only
	Shifting connections hypothesis
		A critical assessment of the hypothesis
			Retinal growth
			Tectal growth
			The projection
		The attack against shifting connections
		Evidence for shifting terminals in axonal trajectories
			Different pattern in chick
	Summary of shifting connections
	References
	Further reading
Specification of the retina and tectum
	Specification of the retina
		Eye rotation and the time of normal specification
			Anatomical problems and inconsistencies
			Revision of amphibian specification
			Contributions of cells from the optic stalk
			Conclusions
		Respecification by other tissues
		Respecification by intraretinal signaling
			Bisected eyes
			Complex compound eyes
			Pie slice compound eyes
		Summary of retinal specification
		Genetic control of expression of NT and DV gradients
			Overview of TF control of specification in retina and tectum
			The NT axis of the retina
			The DV axis of the retina
	Specification of the tectum
		Is the tectum recognized by retinal axons?
		Tectal grafts in the adult demonstrate tectal specification
		Embryonic tectal rotations and the origins of tectal specification
			Tectal rotations in Xenopus embryos
			Embryonic tectal rotations in chick
			Summary
		Genetic control of the AP axis in tectum
			Engrailed and EphA/ephrinA expression in tectum
			What controls the ML axis in tectum?
		Summary and conclusions
	References
Development of the visual pathways
	Morphogenesis of the optic cup and optic stalk
	Axonal outgrowth: Pathfinding within retina
		Morphological analysis
		How much directional information is necessary for the axon to reach the ONH?
		Blueprint hypothesis: Oriented spaces and structural substrates
		Blueprint hypothesis: Neural cell adhesion molecule and laminin
		Blueprint hyposthesis: Growth-inhibiting matrix elements
		Attraction by Shh gradients: Growth-promoting effects
		Molecular factors in retinal axon fasciculation
		EphB receptors selectively affect dorsal axons at the ONH
		Role of pathfinders and followers
		Netrin-1 attracts axons into the ONH
	Growth and order of axons in the optic nerve and tract
		Fish: Highly ordered organization
		How ordered is the optic nerve across vertebrate classes?
		Errant paths at chiasm and corrections during development
		Reorganization after the chiasm
		Molecular components promoting growth in the optic stalk
		Molecular guidance at the optic chiasm: The slit guardrail
		Molecular guidance at the optic chiasm: HSPG and CSPG
		Molecular guidance at the optic chiasm: Shh inhibitory effects at chiasm
		Positive factors at chiasm
		Summary
	The ipsilateral RT projection from the ventrotemporal axons in mammals
	Initial retinotectal projection to tectum
		Xenopus
		Fish
		Chick
		Rodents
		General conclusions on initial innervation
	The contributions of pathway guidance
	References
	Further reading
Genetic analysis of molecular gradients defining map formation
	Introduction
	Genetic analysis of the AP axis of the map: The gradients of EphA in retina and of ephrinA in tectum
		Knockouts and misexpression show roles for ephrinA2 and A5 (Elf-1 and RAGS)
		Knockouts and misexpression show roles for retinal EphAs
		The simple model and the complexity produced by countergradients in retina and tectum
		Reverse signaling, and its contributions
		Mechanism of reverse signaling involves neurotrophins
		Importance of relative vs absolute levels of EphAs and ephrinAs
		Models based explicitly on all EphA and ephrinA forward and reverse interactions
		The map reversal problem with the ipsilateral retinotectal projections
		Conclusions
	DV axis: The gradients of Eph B receptor family in retina and of ephrinB ligand family in tectum
		EphB receptor and ephrinB ligand gradients
		Knockouts and misexpression demonstrate forward attraction
		Reverse signaling via ephrinB2 also mediates attraction
		A model of dual (forward and reverse) attraction signaling
		Wnt signaling for the DV axis in chick
		Semaphorin3D signaling via neuropilin
		Conclusions
	References
Activity-driven synaptic stabilization
	Early studies on nicotinic acetylcholine receptors, α -bungarotoxin, and synapse stabilization
		Initial suggestion of nicotinic transmission turns out to be strong modulation
		Effects of local α BTX on the retinotectal map
		Evidence for glutamatergic transmission and presynaptic cholinergic modulation
		Nucleus isthmi is the source of cholinergic modulation
		Alpha7 AChRs and Ca + + entry facilitate NT release
	Activity-dependent map sharpening via NMDA receptors
		Role of activity in retinotopic sharpening—Regeneration
			Blocking activity with tetrodotoxin
			The role of correlated activity—Strobe experiments
			The role of NMDA receptors in sharpening
		Role of activity in retinotopic sharpening—Development
			Studies in frog and fish
			Spontaneous activity waves in mammalian retina drive sharpening
			Interaction with EphA-ephrinA gradient system
			Conclusions
	The role of activity in sensory map alignments—Several cases with a common theme
		The indirect ipsilateral retinotectal projection in frogs
		Binocular cortical neurons in the mammalian geniculocortical system
		Formation of congruent corticotectal and retinotectal maps
		Aligning the auditory with the visual map in the tectum
	The role of activity in eye specific segregation
		Segregation in different systems—One mechanism
		Role for NMDA receptors in frog
		A transient chick RT ipsilateral projection
		Mammals—Segregation via activity waves
	References
	Further reading
Activity: Molecular signaling to growth mechanisms
	Introduction
	Dynamic analysis of arbor growth
		Blocking NMDA receptors increases branch formation and deletion
		Presence of a synapse stabilizes its branch
		Branches added near synapses
		Relative activity regulates arbor size
	Plasticity mechanisms linked to LTP and LTD
		The Xenopus retinotectal model of LTP induction
		LTP can be induced by visual activity and can affect postsynaptic response properties
		Lisman model of plasticity: NMDAR, cam kinase II, cAMP-dep kinase and phosphatases
		How is Xenopus LTP maintained or reversed after induction?
	CamKII and growth control in Xenopus
		Overexpression of CaMKII activity slows retinal arbor growth
		Inhibiting CaMKII activity increases retinal arbor growth
		Growth rates drop with maturation and accumulation of CaMKII in tectal neurons
	LTP and LTD coupled to retrograde signaling in Xenopus
		LTP and BDNF effects in Xenopus tectum
		LTD and NO effects in Xenopus tectum
	LTP and LTD in mammalian tectum
		Time course of LTP and LTD in rat tectum
		Mechanisms of LTP and LTD in rat tectum
		Relationship of LTP and LTD to activity-dependent retinotopic refinement
	LTD, retraction, and the NO signal in rodent tectum
		Evidence linking LTD with NO as the retrograde signal for retraction of the errant collaterals
		NO signaling for retractions in other visual projections
		Exempting retinotopic synapses from NO-mediated retraction
	LTP and BDNF effects in rodent and frog tectum
		BDNF role in LTP at the presynaptic terminals
		BDNF—Role in LTP on the postsynaptic side
		BDNF—Role in LTP at the presynaptic terminals
		LTP and BDNF interact with ephrinB reverse signaling at presynaptic terminals
		Summary
	Homeostatic control of synaptic plasticity and regulation of the sensitive period
		Homeostatic control of synaptic plasticity by neuroimmune proteins
		Regulation of the sensitive periods for visual plasticity
	F-actin-based growth-control mechanisms
		Relationship to synapse formation and stabilization
		Wider view—F-actin-based axon growth mechanism
			Summary of the rho mechanisms
			BDNF effects on p250 GAP
		How CAMs stimulate growth in axons
		AA as a Ca + + stimulated retrograde synaptic signal downstream of NMDARs
		AA targets presynaptic cPKC β for growth modulation via GAP43
		The polarity complex and PI3 kinase control branching
			Polarity complex
			PI3 kinase
			Other branching cues
			Control of lamination
	Summary of growth-control mechanisms
	References
Summary of mechanisms generating the retinotectal map
	Introduction
	Results so far demonstrate little or no contribution from three types of mechanism
		Rigid chemoaffinity does not determine the map
		Connections are not based on the timing of the birth of neurons or their axons’ arrival at tectum
		Selective fiber-fiber homophilic adhesion for pathway ordering has not been directly demonstrated to contribute to the RT map
	Four main mechanisms contribute to map formation
		Molecular gradients along the AP and DV axes
			Molecular gradients of EphA, ephrinAs provide intratectal guidance along AP axis
			EphB and ephrinBs guide along the ML axis along with other gradients
		Pathway ordering contributes to the DV to ML axis of the RT map
		Activity-driven mechanisms provide fine-scale refinement of the maps
		Competition: Does it work through activity, through ephrin/Eph interactions or is it independent?
	Basic differences arose between anamniotes and amniotes necessitating modifications of mechanisms
		Small vs large tissues at time of initial innervation
		Sequential vs simultaneous innervation by retinal axons
		Small vs large errors in retinal fiber branching
		Activity-driven sharpening using visual experience vs without vision using activity waves
		Continued plasticity vs closing of developmental sensitive period
	These rules apply to other visual and nonvisual maps
	Successful models incorporate fiber-target and fiber-fiber gradient signaling as well as activity mechanisms
	Contributions of models in testing mechanisms and generating further experiments
	References
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