| Program#/Poster#: |
914.15/MMM31 |
| Title: |
Hebbian and neuromodulatory mechanisms
act synergistically to instruct associative memory formation |
| Location: |
Halls B-H |
| Presentation Time: |
Wednesday, Nov 17, 2010, 3:00 PM - 4:00
PM |
| Authors: |
*J. P. JOHANSEN1,
H. HAMANAKA2, L. DIAZ-MATAIX2,
J. E. LEDOUX2,3;
1Ctr. for Neural Sci., New York Univ., NEW YORK, NY; 2Ctr. for Neural Sci.,
New York Univ. New York, NY 10003, USA, New York, NY; 3Orangeburg, Nathan
S. Kline Inst. for Psychiatric Res., New York, NY |
| Abstract: |
Fear conditioning is a form of associative
learning in which organisms acquire defensive responses to sensory stimuli
that predict impending danger. The lateral nucleus of the amygdala (LA)
is a site of associative plasticity for fear memory storage and it is generally
believed that this results from a Hebbian process whereby US-evoked depolarization
of LA pyramidal neurons instructs plasticity at synapses formed by weaker,
coactive CS inputs onto the same neurons. However, other theories of synaptic
plasticity suggest that memory storage is engaged through activation of
multiple processes including Hebbian mechanisms (depolarization) combined
with neuromodulatory influences (Bailey et al, 2000). To test whether depolarization
of LA neurons is sufficient as a US to produce fear learning we expressed
the light activated channelrhodopsin (ChR2) specifically in LA pyramidal
neurons using an adeno-associated viral vector. We then paired an auditory
CS with direct laser light stimulation of LA pyramidal neurons as a US,
in the absence of a peripheral shock US. This training regimen produced
fear conditioning but was not optimal as standard training conditions (3
CS-US pairings) produced no fear learning while large numbers of pairings
resulted in low levels of conditioning. However, when conditioning was performed
with a dual US that included weak footshock (which alone produced little
conditioning) in combination with laser depolarization of LA pyramidal neurons
specifically during the US period, supra-additive levels of fear conditioning
occurred (compared with laser stimulation or weak shock alone). This effect
was blocked if a noradrenergic ?-receptor (?-AR) antagonist (propanolol,
0.12 ug in 0.3 uL) was infused into the LA prior to conditioning, suggesting
that the weak shock US contributed to fear conditioning by stimulating ?-ARs
in the LA. To directly test this hypothesis we infused a ?-AR agonist (isoproteronol,
1.5 ug in 0.3 uL) into the LA and then performed fear conditioning by pairing
the auditory CS with the laser stimulation US in the absence of a footshock
US. Whereas neither the ?-AR agonist nor laser stimulation US alone produced
learning, combined laser stimulation and ?-AR activation did produce fear
memory formation. These findings demonstrate that conjoint depolarization
of LA pyramidal cells (as a US) and LA ?-AR activation is sufficient to
reinforce fear conditioning and support the idea that associative memory
formation is governed by a multi-process model in which both Hebbian and
neuromodulatory processes are essential. |
| Support: |
NRSA fellowship F32-MH082505
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NIH grant R01-MH46516 |
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