Grades for Exam I BCS 249 Range: 30-96 Average: 71 Before curve: After curve: w/ curve 85-87: A- 82-84: B+ 78-81: B 75-77: B- 72-74: C+ 68-71: C 65-67: C- 62-64: D+ 58-61: D 55-57: D- 0-54: F Range: 30-96 Average: 71

Optional short presentations in class April 26th & May 1st: -research a human neurological disorder or injury and discuss in the context of developmental neurobiology -give a short 5-10 min slide presentation -write a 5-page report on how altered neural development may contribute/contributes to the disease, and which form of therapy you would recommend Examples: -Huntington’s chorea -Alzheimer’s disease -Major depressive disorder -Schizophrenia -Traumatic brain injury

Retinal cell outgrowth on tectal membranes expressing EphrinA ligands: no temporal growth

EphA2-/-; A5-/- RGCs randomly project to tectum; ectopic EphA3 R causes anterior shift of projections

Gradients of both ligand (tectum) and receptor (axon) establish map

Ephrins & EphR gradients shape the retinotectal map across species

Retinal axon outgrowth is promoted at low levels of Ephrin-A2 even the temporal RGCs will extend neurites in low levels of ephrin-A2 ligand

Repulsive EphA signals guide retina N-T, tectum A-P axon mapping; attractive EphB signals guide D-V, D-V axon mapping Xenopus laevis (frog)

EphrinA ligands activate EphA receptors, & EphrinBs activate EphB receptors

High EphA (T ret) low EphrinA (A tect); high EphB (V ret) high EphrinB1 (M tect) EphA-ephrinA: repulsive guidance EphB-ephrinB: attractive guidance

EphrinB-EphB forward & reverse signaling in D-V retinotectal map p154: retina expresses ephrin ligand and EphB receptor; dorsal retina ligand is attracted to its receptor in the tectum (=reverse signaling from R  ligand); forward signaling occurs betw. V retina & M tectum (chick & mouse)

The tectum/colliculus develops from progenitors between midbrain & hindbrain p32: How is the brain & tectum specified? MB-HB organizer, Engr1 expression is the marker at the MB-HB border. Otx2 is expressed in the MB, & Gbx2 is expressed in the HB.

Grafting experiment demonstrates a midbrain-hindbrain organizer Alvarado-Mallart transplanted a bit of quail MB-HB tissue to a chick brain, & the chick brain generated a second cerebellum, as well as an ectopic midbrain.

Fgf8: a potent signal within the MB-HB organizer

Fgf8 bead duplicates the organizer region & mesencephalon in the diencephalon Fgf8 bead induces graded expression of Engrailed

Olfactory receptor neurons synapse with 2nd order neurons in the glomerulus

Each glomerulus in the olfactory bulb receives neurons of only one subtype Brain  Nose 

Topographic map in the olfactory epithelium is random (grouped by odorant)

Genetic labeling of an olfactory receptor revealed convergence on one glomerulus P2 receptor+ cells= blue This labeling study led to the hypothesis that targeting is achieved by growth cone expression of the olfactory receptor, with its attracting ligand localized to the glomerulus

Olfactory receptors are expressed on both dendrites and axons epithelium olfactory bulb (brain) Odorant receptor protein is expressed on both dendrites and axons of olfactory sensory neurons. A and B. Staining of mouse olfactory epithelium with antibodies to two different particular odorant receptors (one labelled in red, the other in green). C. and D. Staining of mouse olfactory bulb with the same antibodies. Scale bars, 10mm. (From Barnea et al., 2004)

No defined regional specificity in the nasal epithelium for olfactory neuron subclasses p 162: Fig 6.24: All olfactory neurons of a specific subtype converge on a single glomerulus in the olfactory bulb of the brain; however, unlike the retina, the neurons are not highly organized spatially within the nasal epithelium

The olfactory neuron subtype & glomerular target is defined by its receptor

P2 receptor deletion causes loss of glomerular targeting Misexpressing the M71 under the control of P2, they do not innervate either the M71 or P2 glomerulus, but a different glomerulus. Deleting P2 leads to complete failure of P2 neurons to innervate any glomerulus.

Swapping M71 in place of the P2 receptor leads to glomerulus “X” targeting p162: Fig 6.24--

Other guidance factors are needed for precise glomerular targeting In addition to the receptor itself, other guidance molecules/cell adhesion molecules are necessary to direct the final step of targeting: swapping P2 & P3, neighboring glomerular receptor subtypes, leads to nearly-precise glomerulus targeting… but not exact.

Fine-tuning synaptic connectivity: A) reducing # afferents/ arborization to multiple target cells p250, Fig.9.1:

Fine-tuning neural connectivity: B) removing redundant inputs (afferents) to the same target cell

In maturing neural circuits: C) remove excess synapses on same neuron p250: remove dendritic synapses, leave only somatic targeting

Synaptic maturation also involves altering # synapses from a specific presynaptic neuron (afferent projection) In this example, A, B, & C each form 4 synapses with the target cell. After rearrangement, A & C form 6 synapses w/ target, and B loses connection with the target cell. The number of synapses on the target cell remains constant, but the neuronal connections are altered.

Dual innervation of muscle by motor neurons is lost postnatally

Multiple innervations at the immature neuromuscular junction Fig. 9.6 p256: Retraction of the blue neuron during postnatal synaptic maturation

Electrophysiological test for number of convergent inputs Fig.9.2 p251: Stimulating electrode placed in afferent field; intracellular recording on postsynaptic cell *quantal increases in PSP amplitude  estimate of input #

The number of convergent innervations decreases with maturity Fig.9.2 p251: examples of decreased afferent convergence during developmental progression