1. EXAM 3 REVIEW Katherine & Tina

2. Developments of Neural Circuits Lecture 19

3. 2 Mechanisms of Development.. Activity Independent – Chemoaffinity Hypothesis (Sperry) form precedes function Experiments: eye-rotation studies; Stripe assay; retinal ablation Mechanisms: Ephrin/Eph Receptors Activity Dependent – Correlation-Based Change (Hebb) Experience shapes the brain Experiments: V1/A1 rewiring; eye specific stripes Mechanism: Synapse Maturation (LTP/Depolarizing GABA); activity dependent gene expression

4. Activity Independent Experiments Eye Rotation in Newt: rotate eye of ADULT newt 180º = sees world upside-down Adult v. Baby? Retinal Ablation: Ablate ½ the retina missing connections in ½ the tectum The persisting retinal half WILL NOT REWIRE to take up the whole tectum Stripe Assay: temporal retinal neurons only grow on membrane stripes from anterior tectum; nasal retinal neurons project through both

5. Activity Independent Mxns Ephrin/EphR Chemical Gradient Ephrin = ligand Eph = receptor

6. Activity Dependent Experiments Rewiring ferret cortex: rewiring retinal projections to MGN (by deafening the ferret) A1 now has V1 features (orientation pinwheels and long horizontal connections) Eye specific stripes: addition of APV (NMDAR inhibitor) loss of eye specific stripe segregation

7. Activity Dependent Mxns Synapse Maturation: visual activity accelerates synaptic maturation Unsilence NMDAR only synapses (LTP) increase AMPAR/NMDAR ratio Depolarizing GABA Gene Expression: activity drives gene expression, affecting dendritic growth and synaptic maturation Cpg15 expression of the gene induces gene maturation

8. Its not as distinct…. Layer IV ocular dominance columns (ODC) development = activity dependent and independent Independent: ODC start to develop before eyes open Dependent: activity required to segregate the columns Activity from spontaneous retinal waves? Ocular dominance shift: Monocularly deprived animals open eyes OD stripes are much larger

9. In summary…. Neural development is influenced by activity independent and dependent factors Independent dictates original structure Dependent refines neural development LTP-like mechanisms But its never completely distinct…

10. Neural Basis of Behavior Dr. Khakhalin Guest Lecture Lecture 18

11. Terms to know FIXED ACTION PATTERN: stereotypic behavior; once initiated, it is executed in its entirety Ex. Egg rolling; sneezing RELEASING STIMULUS: triggering stimuli; object that induces certain behaviors/responses Ex. Red spot (seagull beak); egg (greylag goose) SUPERNORMAL STIMULUS: stimulus that works better than a real or normal stimuli Ex. Full red beak; giant eggs

12. Teleost Fish Escape Circuit Major features of this circuit: Allows the fish to flee in the the correct direction The M Cell only fires once (doesnt swim in circles) Has a threshold

13. Teleost Fish Escape Circuit Major features of this circuit: Allows the fish to flee in the the correct direction The M Cell only fires once (doesnt swim in circles) Has a threshold

14. Stimulus: Sound or vibrations in water CN VIII is activated M cell is excited sends excitatory signals down axon Excitatory signals activate contralateral motor neuron, which then contracts the contralateral muscle Excitatory signals also activate contralateral inhibitory interneurons, which send inhibitory signals to the ipsilateral motor neuron

15. Teleost Fish Escape Circuit Major features of this circuit: Allows the fish to flee in the the correct direction The M Cell only fires once (doesnt swim in circles) Has a threshold

16. Feedback inhibition (ipsilateral)

17. Stimulus: Sound or vibrations in water CN VIII is activated M cell is excited sends excitatory signals down axon Excitatory signals also activate ipsilateral inhibitory interneurons, which send inhibitory signals to the ipsilateral M cell vial chemical and electrical (axon cap) means

18. Teleost Fish Escape Circuit Major features of this circuit: Allows the fish to flee in the the correct direction The M Cell only fires once (doesnt swim in circles) Has a threshold

19. Feedforward inhibition (contralateral)

20. Stimulus: Sound or vibrations in water CN VIII is activated Contralateral PHP interneuron inhibits the contralateral M cell CN VIII activates inhibitory PHP interneurons Ipsilateral PHP interneuron inhibits the ipsilateral M cell through the axon cap

21. Paper 2: Haas et al.

22. Hypothesis Transient dendritic branches sample the local environment for appropriate contact sites and then stabilize to form mature synapses. AMPAR activity is required for dendritic arbor growth Looking to see if AMPAR are required for the stabilization/growth of dendritic synapses and branches

23. Figure 1 Tests the effectiveness of their gene constructs in reducing AMPAR-mediated transmission Constructs efficiently decrease AMPAR transmission

24. Figure 2 Disrupting AMPAR transmission reduction in overall dendritic growth/growth rate(A and B) and dendritic branching (C and D)

25. Figure 3 Disrupting AMPAR transmission reduces dendrite branch stability Branches in R1/R2 neurons are more dynamic More branches are retracted Rate of retraction is faster Branches have shorter lifespan R1/R2 = Less Stable

26. Figure 4 AMPAR transmission is necessary for proper maturation of synapses R1/R2 cells have lower Ac/At ratios (similar in value to Ac/At ratios of S39, immature neurons)

27. Figure 5 AMPAR transmission is required for experience dependent structural plasticity R1/R2 dendrites decreased in arbor length and number of branch tips upon visual stimulation

28. Dendritic Function (Active Properties) Lecture 13

29. Active Membrane Properties VOLTAGE GATED CHANNELS Dendrites = generate spikes that boost their signals Spikes = current entering into cell from VG Na+, Ca+2 or K+ channels Can be activated by sub-threshold EPSPs

30. Voltage Gated Channels Different neurons = different expression patterns of VG channels Hippocampal pyramidal neuron = more dendritic Na+ channels Perkinje neurons = few Na+ channels, lots of Ca+2 Na+ channels = proximal; Ca+2 = distal

31. Summation Active dendrites can result in NON-LINEAR SUMMATION OF EPSPs Active dendrites can also affect the interaction between Excitation and Inhibition o depends on location of inputs (within the same branch or between branches)

32. Backpropogation Dendrites can actively backpropogate signals from the soma (soma dendrite) o regulated by VG Na+ channels (addition of TTX = lose backpropogation signal) o Somatic AP backpropogate open channels = increase dendritic Ca+2 levels