1. Schedule for remaining classes: 4/11/16: 3 rd learning/memory, intro to sex differentiation in nervous system development 4/13/16: Sex differentiation in nervous system development; intro to Presenilins and Alzheimer’s disease 4/18/16: Dr. Doug Portman– genetic sex determination in the nervous system 4/20/16: Presenilins from development to neurodegeneration 4/25/16: Presentations (1hr), with short review session 4/27/16: Exam 3 5/2/16 (9-11:30): Presentations 5/4/16 (9:30-11:30): Presentations

2. LFS: <0.1 Hz HFS: 100 Hz (brief) Long-term potentiation: functional model for explicit memory *increased EPSP amplitude maintained for >60 min

3. Long-term potentiation in CA1 is highly afferent-specific

4. Cooperativity: activation of multiple afferents (NMDAR- dep) Synapse selectivity: only the active afferents will be potentiated Associative: requires simultaneous pre/post activity to depolarize postsynaptic cell LTP in the Schaffer collateral pathway requires:

5. Spaced stimuli give larger sustained EPSP amplitude (LTP) vs. one tetanic stimulation

6. Hippocampal neuron LTP requires simultaneous afferent activity and postsynaptic depolarization

7. CamKII Postsynaptic depolarization activates CamKII & leads to greater numbers of AMPARs in postsynaptic membrane

8. CaMKII activity is regulated by Ca 2+ -calmodulin binding to release regulatory “hinge”

9. LTP may not rely solely upon new AMPAR insertion, but also enhanced NT release probability

10. The number of NT release events increases after LTP induction

11. Multiple spaced trains, or stimuli, leads to late-phase LTP; one train evokes smaller increase in EPSP for less time

12. Genetic blockade of PKA eliminates late-phase LTP

13. Early-phase LTP does not require CREB activation, synapse growth

14. Synaptic structural changes in L-LTP include new AZs, PSDs

15. Similar to LTP, long-term depression (LTD) is afferent-specific in CA1 *low-freq tetanus

16. Different levels of Ca 2+ influx activate either kinase or phosphatase activity at the postsynaptic terminal

17. Amount of NMDAR activation correlates positively w/ LTP & negatively w/ LTD

18. Govindarajan et al. Nature Reviews Neuroscience 7, 575–583 (July 2006) | doi:10.1038/nrn1937 *capture associativity betw.1-2 and 3 3: L-LTD 1,2: L-LTP LTP and LTD proteins are generated in response to LTP stimuli & influence plasticity of nearby synapses potentiation tags capture LTP proteins

19. The Morris water maze learning & memory test requires NMDAR

20. Transcriptional control by enhancers and repressors

21. promoter Conditional deletion of NMDA R1 subunit (NR1) in CA1 neurons by Cre-lox

22. CA1-specific Cre; NR1 cKO mice have defective LTP, memory

23. promoterMutant gene Constitutive activation of CaMKII kinase until Dox shuts it off

24. Persistent activity of CaMKII interferes w/ learning & converts LTP to LTD

25. Hormone-dependent sexual differentiation in the nervous system

26. Testis-determining factor (TDF, aka SRY) changes the default ovary-generating program SRY: SOX homeobox TF, upregulates other TFs  seminiferous tubules

27. before testes: Mullerian & Wolffian ducts Reproductive system is generated intersex and becomes specified by hormones

28. Gonadotropin-releasing hormone in hypothalamus releases FSH, LH from pituitary GnRH1: essential for both ovulation (female) & spermatogenesis (male) testosterone: prohormone for DHT, estradiol

29. Estradiol, essential for masculinization of the rat brain, has many receptors in the POA and anterior hypothalamus

30. Neurosecretory cells in hypothalamus stimulate/inhibit pituitary hormone release via pituitary capillary bed

31. Estradiol surge causes high LH, FSH at ovulation

32. Castration + estrogen leads to female behavior; testosterone in female causes male behavior

33. Testosterone is converted to estrogen by aromatase; estrogen binds to ER and regulates transcription

34. psych.unn.ac.uk

36. The spinal nucleus of the bulbocavernosus: sexually dimorphic neurons innervating the perineal muscles

37. Females have very few SNB motoneurons, perineal muscles

38. Injecting female with testosterone causes sparing of SNB neurons, perineal muscles

39. Castration + androgen blocker in males: female-like SNB, perineal muscles