Abstract
Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysregulation of miR-132 has been suggested to play a role in a number of neurocognitive disorders characterized by aberrant synaptogenesis. However, little is known about the inducible expression and function of miR-132 under normal physiological conditions in vivo. Here, we begin to explore this question within the context of learning and memory. Using in situ hybridization, we show that the presentation of a spatial memory task induced a significant ~1.5-fold increase in miR-132 expression within the CA1, CA3, and GCL excitatory cell layers of the hippocampus. To examine the role of miR-132 in hippocampal-dependent learning and memory, we employ a doxycycline-regulated miR-132 transgenic mouse strain to drive varying levels of transgenic miR-132 expression. These studies revealed that relatively low levels of transgenic miR-132 expression, paralleling the level of expression in the hippocampus following a spatial memory task, significantly enhanced cognitive capacity. In contrast, higher (supra-physiological) levels of miR-132 (>3-fold) inhibited learning. Interestingly, both the impaired cognition and elevated levels of dendritic spines resulting from supra-physiological levels of transgenic miR-132 were reversed by doxycycline suppression of transgene expression. Together, these data indicate that miR-132 functions as a key activity-dependent regulator of cognition, and that miR-132 expression must be maintained within a limited range to ensure normal learning and memory formation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 817-831 |
| Number of pages | 15 |
| Journal | Brain Structure and Function |
| Volume | 218 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 2013 |
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Keywords
- CREB
- Hippocampus
- Learning
- Memory
- miRNA
- Neuronal plasticity
ASJC Scopus subject areas
- Anatomy
- Histology
- Neuroscience(all)
Cite this
MiRNA-132 : A dynamic regulator of cognitive capacity. / Hansen, Katelin F.; Karelina, Kate; Sakamoto, Kensuke; Wayman, Gary A.; Impey, Soren; Obrietan, Karl.
In: Brain Structure and Function, Vol. 218, No. 3, 05.2013, p. 817-831.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MiRNA-132
T2 - A dynamic regulator of cognitive capacity
AU - Hansen, Katelin F.
AU - Karelina, Kate
AU - Sakamoto, Kensuke
AU - Wayman, Gary A.
AU - Impey, Soren
AU - Obrietan, Karl
PY - 2013/5
Y1 - 2013/5
N2 - Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysregulation of miR-132 has been suggested to play a role in a number of neurocognitive disorders characterized by aberrant synaptogenesis. However, little is known about the inducible expression and function of miR-132 under normal physiological conditions in vivo. Here, we begin to explore this question within the context of learning and memory. Using in situ hybridization, we show that the presentation of a spatial memory task induced a significant ~1.5-fold increase in miR-132 expression within the CA1, CA3, and GCL excitatory cell layers of the hippocampus. To examine the role of miR-132 in hippocampal-dependent learning and memory, we employ a doxycycline-regulated miR-132 transgenic mouse strain to drive varying levels of transgenic miR-132 expression. These studies revealed that relatively low levels of transgenic miR-132 expression, paralleling the level of expression in the hippocampus following a spatial memory task, significantly enhanced cognitive capacity. In contrast, higher (supra-physiological) levels of miR-132 (>3-fold) inhibited learning. Interestingly, both the impaired cognition and elevated levels of dendritic spines resulting from supra-physiological levels of transgenic miR-132 were reversed by doxycycline suppression of transgene expression. Together, these data indicate that miR-132 functions as a key activity-dependent regulator of cognition, and that miR-132 expression must be maintained within a limited range to ensure normal learning and memory formation.
AB - Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysregulation of miR-132 has been suggested to play a role in a number of neurocognitive disorders characterized by aberrant synaptogenesis. However, little is known about the inducible expression and function of miR-132 under normal physiological conditions in vivo. Here, we begin to explore this question within the context of learning and memory. Using in situ hybridization, we show that the presentation of a spatial memory task induced a significant ~1.5-fold increase in miR-132 expression within the CA1, CA3, and GCL excitatory cell layers of the hippocampus. To examine the role of miR-132 in hippocampal-dependent learning and memory, we employ a doxycycline-regulated miR-132 transgenic mouse strain to drive varying levels of transgenic miR-132 expression. These studies revealed that relatively low levels of transgenic miR-132 expression, paralleling the level of expression in the hippocampus following a spatial memory task, significantly enhanced cognitive capacity. In contrast, higher (supra-physiological) levels of miR-132 (>3-fold) inhibited learning. Interestingly, both the impaired cognition and elevated levels of dendritic spines resulting from supra-physiological levels of transgenic miR-132 were reversed by doxycycline suppression of transgene expression. Together, these data indicate that miR-132 functions as a key activity-dependent regulator of cognition, and that miR-132 expression must be maintained within a limited range to ensure normal learning and memory formation.
KW - CREB
KW - Hippocampus
KW - Learning
KW - Memory
KW - miRNA
KW - Neuronal plasticity
UR - http://www.scopus.com/inward/record.url?scp=84879552488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879552488&partnerID=8YFLogxK
U2 - 10.1007/s00429-012-0431-4
DO - 10.1007/s00429-012-0431-4
M3 - Article
VL - 218
SP - 817
EP - 831
JO - Zeitschrift fur Anatomie und Entwicklungsgeschichte
JF - Zeitschrift fur Anatomie und Entwicklungsgeschichte
SN - 0177-5154
IS - 3
ER -