Damage to the Lateral and Central, but Not Other, Amygdaloid Nuclei Prevents the Acquisition of Audi

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Damage to the Lateral and Central,but Not Other,
Amygdaloid Nuclei Preventsthe Acquisition of
Auditory Fear ConditioningPresented By
Sandeep Kahlon

• Karim Nader, Pedram Majidishad, Prin Amorapanth,
  and Joseph E. LeDoux

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Background Information

• It is believed that the neural circuits
  underlying Pavlovian conditioning involve the
  transmission of the conditioned stimulus to the
  lateral nucleus of the amygdala (LA) which
  controls the conditioned fear responses by way of
  projections from the central nucleus of the
  amygdala (CE) to the brainstem areas.
• Previous research has shown that lesions of the
  LA and the CE prevents fear conditioning.
• However, there are other routes within the
  amygdala through which the LA can act to reach
  the CE, such as the basal (B), accessory basal
  (AB) and medial nuclei (M) which each project to
  the CE.
• Previous studies have made large lesions to areas
  of the basolateral complex which includes the LA,
  B and sometimes the AB and have shown that these
  lesions blocked the acquisition of fear
  conditioning.
• However, damage to the LA alone disrupts fear
  conditioning and the roles of B and AB in fear
  conditioning cannot be concluded from these
  studies.
• In one previous study, damage to the B alone
  seemed to have no affect

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Research Question

• Which areas within the amygdala were found to
  contribute the most to Pavlovian fear
  conditioning?

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Methods

• Subjects
• All subjects were adult male Sprague-Dawley rats
  housed in pairs in Plexiglass cages and were kept
  on a 12-hour light-dark cycle with lights on at
  730 am.
• Rats had ad libitum access to food and water
  during the experiment.
• Rats were undisturbed in their cages for five
  days after which they were handled for five days
  after the experiments were begun.
• Surgery
• Rats were injected with 0.15 cc atropine
  intraperitoneally, anaesthetized with Nembutal
  and placed in a stereotaxic frame.
• A stainless steel electrode insulated with epoxy
  except at its tip was lowered to the target brain
  area and lesions were made by passing positive
  current of various durations through the
  electrode at each lesion site.
• A control group of rats received sham lesions in
  which the electrode was placed 1-1.5 mm dorsal to
  the experimental group and no current was passed.
  
• Lesions were made bilaterally in the LA, CE, B,
  AB, or M. Additional groups received combined
  lesions of the B and AB. A last group received
  lesions that destroyed the entire amygdala.

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Methods Continued

• Rats were habituated to chamber A (the fear
  conditioning chamber) and chamber B (where
  testing would take place) over a 2-day period in
  a counterbalanced order after which testing took
  place.
• Classical conditioning trials took place over a
  2-day period in which the CS was a10-kHz tone and
  the US was a 0.5 sec scrambled shock delivered
  through the floor grid.
• Paired fear conditioning included presenting the
  CS for 20 sec through a speaker and the US
  coterminated with the CS. Paired training
  occurred for all rats given lesions.
• There was also unpaired fear conditioning in
  which the US was presented pseudorandomly and did
  not occur within 60 sec of the CS.
• On day 3 testing took place in which the rats
  were placed in chamber B and allowed to explore
  for about 10 minutes after which the CS was
  presented for 60 sec
• The number of seconds spent freezing (defined as
  immobility except for breathing) during CS
  presentation was determined by observing the
  videotape of the rats behavior.
• The duration of freezing during the CS was
  compared to the duration of freezing in the
  60-sec period just before the onset of the CS
  (pre-CS period).
• Following the behavioral studies rats were killed
  and their brains were analyzed.

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Results

• Little freezing occurred during the pre-CS period
  in any of the groups.
• In the unoperated and sham operated controls
  given paired training much of the 60 sec test was
  accounted for by freezing.
• Those rats that were not operated on and received
  unpaired training exhibited very little freezing.
  
• Freezing during the CS was greatly reduced
  compared to the controls in the groups with large
  amygdala lesions.
• Those rats who received lesions in the LA or CE
  also exhibited a high amount of freezing as
  compared to the control groups.
• Lesions of the basal (B), accessory basal (AB),
  or Medial nucleus (M) had no observable effect on
  the behavior of the rats
• Lesions of the group of rats receiving combined
  damage to the B and AB also showed no observable
  effects on the behavior of rats during the
  testing condition

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The effects of pretraining lesions on the
acquisition ofconditioned freezing behavior
elicited by a Tone.

• From this diagram it can be seen that lesions to
  the entire amygdala, CE and LA had the greatest
  effects on the freezing behavior of the rats to
  the CS during the testing phase.
• Lesions to the B, AB, M and BAB had no obvious
  effects on freezing behavior

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Lesion Diagrams
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Lesion Diagrams Continued
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Discussion

• These findings are consistent with previous
  studies which show that damage to the LA and CE
  disrupts conditioned fear responses.
• The fact that damage to the B, AB, M, B and AB
  together fail to interfere with fear conditioning
  is a very strong indicator that the LA and CE
  alone are sufficient enough to elicit the fear
  response.
• Because of this it is possible that the direct
  connections from the LA to the CE rather than
  indirect pathways involving other nuclei are
  necessary for fear conditioning.
• It is also possible that information from the LA
  can use redundant pathways or indirect routes to
  the CE to engage the freezing response.
• Although the lesions to all other areas except
  the LA and CE had no effect on fear behavior it
  is possible that they are needed in the intact
  brain.
• For example, lesions of B but not CE block the
  acquisition of the instrumental learning using an
  escape from fear task.

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Discussion Continued

• The authors suggest that the reasons why the LA
  and CE block fear conditioning are different.
• Lesions of the LA block fear conditioning because
  this is the site of plasticity mediating
  learning. Lesions of the CE block fear
  conditioning because this is the motor output
  through which learned information needs to access
  the circuits controlling freezing.
• To test this possibility if the other nuclei
  lesioned in this study are necessary in fear in
  intact brains the authors suggest to selectively
  disrupt the pathway from the LA to the CE and
  then test the role of these regions. However,
  this type experiment is very difficult to do
  given the techniques currently available.
• Finally, it is important to note that the results
  found from this study cannot be generalized to
  contextual fear conditioning as this requires
  connections from the hippocampus to the amygdala
  and main projections in the hippocampus terminate
  in the B, AB and CE.

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Question and Answer Recap

• Question
• Which areas within the amygdala were found to
  contribute the most to Pavlovian fear
  conditioning?
• Answer
• The Lateral Nucleus of the amygdala and the
  Central Nucleus of the Amygdala are most involved
  in the Pavlovian fear response.