Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0598853 (
forgetting
)
3,232
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The control of memory retention is important for proper responses to constantly changing environments, but the regulatory mechanisms underlying
forgetting
have not been fully elucidated. Our genetic analyses in C. elegans revealed that mutants of the TIR-1/
JNK
-1 pathway exhibited prolonged retention of olfactory adaptation and salt chemotaxis learning. In olfactory adaptation, conditioning induces attenuation of odor-evoked Ca(2+) responses in olfactory neurons, and this attenuation is prolonged in the TIR-1/
JNK
-1-pathway mutant animals. We also found that a pair of neurons in which the pathway functions is required for the acceleration of
forgetting
, but not for sensation or adaptation, in wild-type animals. In addition, the neurosecretion from these cells is important for the acceleration of
forgetting
. Therefore, we propose that these neurons accelerate
forgetting
through the TIR-1/
JNK
-1 pathway by sending signals that directly or indirectly stimulate
forgetting
.
...
PMID:Forgetting in C. elegans is accelerated by neuronal communication via the TIR-1/JNK-1 pathway. 2352 51
Forgetting
memories is important for animals to properly respond to continuously changing environments. To elucidate the mechanisms of
forgetting
, we used one of the behavioral plasticities of
Caenorhabditis elegans
hermaphrodite, olfactory adaptation to an attractive odorant, diacetyl, as a simple model of learning. In
C. elegans,
the TIR-1/
JNK
-1 pathway accelerates
forgetting
of olfactory adaptation by facilitating neural secretion from AWC sensory neurons. In this study, to identify the downstream effectors of the TIR-1/
JNK
-1 pathway, we conducted a genetic screen for suppressors of the gain-of-function mutant of
tir-1
(
ok1052
), which shows excessive
forgetting
. Our screening showed that three proteins-a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2; and its putative ligand, HEN-1-regulated
forgetting
downstream of the TIR-1/
JNK
-1 pathway. We further demonstrated that MACO-1 and SCD-2/HEN-1 functioned in parallel genetic pathways, and only MACO-1 regulated
forgetting
of olfactory adaptation to isoamyl alcohol, which is an attractive odorant sensed by different types of sensory neurons. In olfactory adaptation, odor-evoked Ca
2+
responses in olfactory neurons are attenuated by conditioning and recovered thereafter. A Ca
2+
imaging study revealed that this attenuation is sustained longer in
maco-1
and
scd-2
mutant animals than in wild-type animals like the TIR-1/
JNK
-1 pathway mutants. Furthermore, temporal silencing by histamine-gated chloride channels revealed that the neuronal activity of AWC neurons after conditioning is important for proper
forgetting
. We propose that distinct signaling pathways, each of which has a specific function, may coordinately and temporally regulate
forgetting
by controlling sensory responses.
SIGNIFICANCE STATEMENT
Active
forgetting
is an important process to understand the whole mechanisms of memories. Recent papers have reported that the noncell autonomous regulations are required for proper
forgetting
in invertebrates. We found that in
Caenorhabditis elegans
hermaphrodite, the noncell autonomous regulations of
forgetting
of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate
forgetting
by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper
forgetting
. We suggest that multiple pathways may coordinately and temporally regulate
forgetting
through control of sensory responses. This study should lead to a better understanding of
forgetting
in higher organisms.
...
PMID:Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in
Caenorhabditis elegans
. 2892 7
