1. Effects of Ventral and Dorsal CA 1 Subregional Lesions on Trace Fear Conditioning J.L. Rogers, M.R. Hunsaker, R.P. Kesner

2. Role of Hippocampus in Pavlovian Fear Conditioning Complete lesions produce deficits in contextual fear. (acquisition and consolidation) Regulates when and where extinction memories are expressed. Necessary for association if stimuli separated in time (trace). –Over time performance depends on prefrontal cortex (PFC).

3. Fear Conditioning Circuitry

4. Contextual Extinction Retrieval

6. Hippocampus Dorsal (posterior - primates) –50% of volume –Preferential role – spatial learning Ventral (Anterior – primates) –50% of volume –Preferential role – anxiety behaviors

8. Major input of visual-spatial information from primary sensory cortical areas is into dorsal subregion. (olfactory evenly distributed) Ventral subregion projects to PFC, dorsal does not. Ventral more closely connected to BNST, Amygdala, and Hypothalamic structures (HPA) Anatomical Connections

10. CA1 subregion involved in temporal pattern association and intermediate-term memory. CA1 pyramidal neurons increase activity during trace conditioning. CA1 NMDA receptors necessary for trace conditioning.

11. Aims Determine if ventral and dorsal CA1 subregion of hippocampus have different roles in trace fear conditioning.

12. Methods 24 Long-Evans rats (4 months, 300-400g) Tested during light phase Stereotaxic infusion of ibotenic acid into dorsal (n = 9) and ventral CA1 (n =7) Controls (n = 8) – vehicle infusions into CA1

13. Ibotenic Acid Toxin produced by Amanita muscaria and Amanita pantherina mushrooms Excitatory Amino acid agonist Damage to adjacent areas, fibers-of-passage, and damage to the vasculature are minimized.

14. Methodological Considerations Excitotoxic lesions can cause over- excitation of “ downstream ” structures – dysfunction of other parts of the circuit. Rats – hippocampus surface area ~1.2cm 2, entire isocortex ~1.5cm 2. Damage to amygdala and cortex. Produce cell death – oxidative stress.

16. Apparatus One used for conditioning and context acquisition Another, without contextual cues or shock, used for retention testing for tone-trace

17. Day1 - AcquisitionDay1 - Acquisition –2 min – 15 trials tone-trace-shock »32s, 10s, 2s (0.5mA) (72s ITI) –Freezing measured during baseline, tone, trace Day 2 –Context retentionDay 2 – Context retention –(24 hrs later) Same chamber, 8 min. without tone, freezing measured every 8s. Day 3 – Tone-trace retentionDay 3 – Tone-trace retention –(48 hrs later) Different chamber, 2min preexposure with 15 tone trace combinations freezing measured every 8s.

18. Context Acquisition

19. Context Test

20. Summary Context Results All groups displayed freezing during ITI of acquisition phase. Ventral CA1 lesion group froze less than dorsal CA1 lesion group and controls. Dorsal CA1 lesion group froze significantly less than controls. Both involved in contextual retention, ventral more.

21. Trace Acquisition

22. Trace Test

23. Summary Trace Results Dorsal and ventral CA1 lesion groups not different from controls during acquisition. Retention – ventral CA1 froze less than controls and dorsal CA1 lesion group, dorsal CA1 lesion group was not different from controls.

24. Tone Acquisition

25. Tone Test

26. Summary Tone Results During acquisition all groups froze during tone. No significant main effect for groups during retention.

27. Conclusions Acquisition not disrupted by CA 1 (d or v) lesions. –May involve entire hippocampus (DG, CA3) Ventral CA 1 “more important” than dorsal CA 1 for retention of context and trace fear memory but dorsal involved. “Mild” deficits to tone retention.