Download Unit 9 Chapter 11

PSYC 3832
NEURAL BASIS OF LEARNING
Week 9
Chapter 11
TIAN YU, PhD
Department of Psychology
College of Liberal Arts and Sciences
A Labile STM Trace Evolves into a Stable LTM
Shortly after an
experience, memory
retrieval is supported by an
active short-term trace. As
this trace decays, a more
stable, long-term memory
trace is generated that can
support memory retrieval
for a much longer period of
time.
The Generic Research Paradigm
This figure illustrates the
generic research design for
determining the contribution of
a particular molecule(s) to
memory storage. A drug or
gene is evaluated by assessing
its effect on memory at two
retention intervals—a short
interval (1 to 2 hours) designed
to assess short-term memory
(STM) and a longer interval,
usually about 24 hours,
designed to assess long-term
memory (LTM).
The Research Paradigm: Hypothetical Outcomes
(A) The drug targeted at Mx impaired performance at the 24-hour
retention interval but had no effect at the 1-hour retention interval.
This result is consistent with the hypothesis that Mx is important for
the consolidation of the long-term memory trace and is not critical for
the short-term memory trace. (B) The treatment impaired
performance at both the 1-hour and 24-hour retention intervals. This
result is consistent with the hypothesis that Mx contributes to both
short-term and long-term memory but is also consistent with other
interpretations.
Transcription and Enduring Memories: CREB
A behavioral experience
such as inhibitory avoidance
training initiates a genomic
signaling cascade that
results in new plasticity
products (mRNA and
protein) needed to
consolidate the memory for
the experience. (Photo
courtesy of James
McGaugh.)
Transcription and Enduring Memories: CREB Deletion
Rusiko
Bourtchouladze
Mice genetically engineered to repress CREB display fear
when tested 3 hours after training but not when tested 24
hours after training. These results are consistent with the
hypothesis that long-term memory but not short-term
memory requires plasticity products transcribed by CREB.
(After Bourtchouladze et al., 1994.)
Transcription and Enduring Memories: CREB Overexpression
This graph illustrates the results
of a long-term memory test
when the inter-trial interval
(ITI)—the time separating light–
shock conditioning trials—was
either 10 seconds or 8 minutes.
Note that long-term memory was
poor when the ITI was 10
seconds compared to when the
ITI was 8 minutes. (B) This
graph shows that injecting a
virus that expresses CREB into
the lateral amygdala (LA) prior to
the conditioning trials can
eliminate the impaired long-term
memory normally found when
the ITI is only 10 seconds.
Translation and Enduring Memories: The De Novo Protein
Synthesis Hypothesis
(A) Anisomycin injected immediately after training disrupts
retention performance at the 6- and 24-hour retention intervals but
not at the 1-hour interval. (B) The effect of anisomycin depends on
the interval between training and the injection. It interfered with
memory formation only when it was given immediately (0 hour)
after training. This result indicates that the consolidation process
was about 3 hours. (After Bourtchouladze et al., 1998.)
The De Novo Protein Synthesis Hypothesis:
Methodological Issues
In addition to blocking protein synthesis, anisomycin has other
effects on neurons. The drug is toxic and can kill neurons. It also
causes an excessive release of neurotransmitters in the region
of the injection and induces genomic signaling cascades in the
neuron that result in an overproduction of mRNAs. These
additional effects make it difficult to accept the conclusion that
the reason anisomycin disrupts memory consolidation is that it
inhibits protein synthesis.
The De Novo Protein Synthesis Hypothesis:
Methodological Issues
Anisomycin directly injected into the brain can prevent the
consolidation of the memory trace. However, these infusions
also have major side effects.
Strong conclusion from the use of general protein synthesis
inhibitors: if the memory is not impaired then it does not
depend on new protein, only on post-translation processes.
Protein Degradation Also Contributes to Memory Consolidation
Protein Degradation Also Contributes to Memory Consolidation
Protein degradation is important for long-term fear memories. (A)
Fear conditioning (FC) induces polyubiquitination in the amygdala.
This process is prevented by the NMDA antagonist ifrenprodil. (B)
The proteasome inhibitor βlactone (βlac) impairs both cued and
contextual fear conditioning. These results indicate that protein
degradation is critical for consolidating long-term fear memories.
(After Jarome et al., 2011.)
Memory Consolidation Processes Operate in at least Three
Waves