Transcript Jeff Barr - USD Biology

Effects of Ventral and Dorsal
CA1 Subregional Lesions on
Trace Fear Conditioning
J.L. Rogers, M.R. Hunsaker, R.P.
Kesner
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).
Fear Conditioning Circuitry
Contextual Extinction Retrieval
Hippocampus
• Dorsal (posterior - primates)
– 50% of volume
– Preferential role – spatial learning
• Ventral (Anterior – primates)
– 50% of volume
– Preferential role – anxiety behaviors
Anatomical Connections
• 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)
• 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.
Aims
• Determine if ventral and dorsal CA1
subregion of hippocampus have different
roles in trace fear conditioning.
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
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.
Methodological Considerations
• 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.
Apparatus
• One used for
conditioning and
context acquisition
• Another, without
contextual cues or
shock, used for
retention testing for
tone-trace
• Day1 - Acquisition
– 2 min – 15 trials tone-trace-shock
» 32s, 10s, 2s (0.5mA) (72s ITI)
– Freezing measured during baseline, tone, trace
• Day 2 – Context retention
– (24 hrs later) Same chamber, 8 min. without
tone, freezing measured every 8s.
• Day 3 – Tone-trace retention
– (48 hrs later) Different chamber, 2min
preexposure with 15 tone trace combinations
freezing measured every 8s.
Context Acquisition
Context Test
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.
Trace Acquisition
Trace Test
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.
Tone Acquisition
Tone Test
Summary Tone Results
• During acquisition all groups froze during
tone.
• No significant main effect for groups during
retention.
Conclusions
• 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.