Effects of Ventral and Effects of Ventral and Dorsal CADorsal CA11

Subregional Lesions Subregional Lesions on Trace Fear on Trace Fear ConditioningConditioningJ.L. Rogers, M.R. J.L. Rogers, M.R.

Hunsaker, R.P. KesnerHunsaker, R.P. Kesner

Role of Hippocampus in Role of Hippocampus in Pavlovian Fear Pavlovian Fear ConditioningConditioning

• 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).

Fear Conditioning Fear Conditioning CircuitryCircuitry

Contextual Extinction Contextual Extinction RetrievalRetrieval

HippocampusHippocampus• Dorsal (posterior - primates)–50% of volume –Preferential role – spatial learning

• Ventral (Anterior – primates)–50% of volume –Preferential role – anxiety

behaviors

• 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 ConnectionsAnatomical Connections

• 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.

AimsAims• Determine if ventral and dorsal

CA1 subregion of hippocampus have different roles in trace fear conditioning.

MethodsMethods• 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

Ibotenic AcidIbotenic Acid• Toxin produced by

Amanita muscaria andAmanita pantherina mushrooms

• Excitatory Amino acid agonist

• Damage to adjacent areas, fibers-of-passage, and damage to the vasculature are minimized.

Methodological Methodological ConsiderationsConsiderations

• Excitotoxic lesions can cause over-excitation of “downstream” structures – dysfunction of other parts of the circuit.

• Rats – hippocampus surface area ~1.2cm2 , entire isocortex ~1.5cm2 .

• Damage to amygdala and cortex. • Produce cell death – oxidative

stress.

ApparatusApparatus• One used for

conditioning and context acquisition

• Another, without contextual cues or shock, used for retention testing for tone-trace

• 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 –Day 2 – Context retentionContext 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.

Context AcquisitionContext Acquisition

Context TestContext Test

Summary Context Summary Context ResultsResults

• 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.

Trace AcquisitionTrace Acquisition

Trace TestTrace Test

Summary Trace Summary Trace ResultsResults

• 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.

Tone AcquisitionTone Acquisition

Tone TestTone Test

Summary Tone ResultsSummary Tone Results

• During acquisition all groups froze during tone.

• No significant main effect for groups during retention.

ConclusionsConclusions• Acquisition not disrupted by CA1 (d

or v) lesions.–May involve entire hippocampus

(DG, CA3)• Ventral CA1 “more important” than

dorsal CA1 for retention of context and trace fear memory but dorsal involved.

• “Mild” deficits to tone retention.