Altered synaptic plasticity and behavioral abnormalities in CNGA3-deficient mice.
The role of the cyclic nucleotide-gated (CNG) channel CNGA3 is well established in cone photoreceptors and guanylyl cyclase-D-expressing olfactory neurons. To assess a potential function of CNGA3 in the mouse amygdala and hippocampus, we examined synaptic plasticity and performed a comparative analysis of spatial learning, fear conditioning and step-down avoidance in wild-type mice and CNGA3 null mutants (CNGA3(-/-) ). CNGA3(-/-) mice showed normal basal synaptic transmission in the amygdala and the hippocampus. However, cornu Ammonis (CA1) hippocampal long-term potentiation (LTP) induced by a strong tetanus was significantly enhanced in CNGA3(-/-) mice as compared with their wild-type littermates. Unlike in the hippocampus, LTP was not significantly altered in the amygdala of CNGA3(-/-) mice. Enhanced hippocampal LTP did not coincide with changes in hippocampus-dependent learning, as both wild-type and mutant mice showed a similar performance in water maze tasks and contextual fear conditioning, except for a trend toward higher step-down latencies in a passive avoidance task. In contrast, CNGA3(-/-) mice showed markedly reduced freezing to the conditioned tone in the amygdala-dependent cued fear conditioning task. In conclusion, our study adds a new entry on the list of physiological functions of the CNGA3 channel. Despite the dissociation between physiological and behavioral parameters, our data describe a so far unrecognized role of CNGA3 in modulation of hippocampal plasticity and amygdala-dependent fear memory.
Michalakis
S
S
Munich Center for Integrated Protein Science, Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandstrasse 5-13, Munich, Germany. michalakis@lmu.de
Kleppisch
T
T
Polta
S A
SA
Wotjak
C T
CT
Koch
S
S
Rammes
G
G
Matt
L
L
Becirovic
E
E
Biel
M
M
D000161:Acoustic Stimulation; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D003863:Depression / Q000235:genetics / Q000523:psychology; D004193:Discrimination Learning / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005239:Fear / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012677:Sensation / Q000502:physiology; D013550:Swimming / Q000523:psychology; D013569:Synapses / Q000502:physiology*
C518237:Cnga3 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels