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1

Impact of fear memory consolidation and retrieval on the mRNA expression of G proteins in mice brain

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Zelek-Molik A., Costanzi M., Rafa-Zablocka K., Kreiner G., Roman A., Cestari V., Nalepa I.
Acta Neurobiologiae Experimentalis
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2017
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tom 77
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nr Suppl.1
INTRODUCTION: Fear evoked signaling disturbances among hippocampus (HP), nuclei of amygdala (Amy) and prefrontal cortex (PFC) underlie anxiety related disorders, but their molecular mechanism remains elusive. Heterotrimeric G proteins (GP) based on intracellular activity of alpha subunit (Gα) are divided into four families: G(s) stimulating cAMP generation; G(i/o) inhibiting cAMP pathway; G(Q/11) increasing Ca++ level; G(12/13) activating monomeric GP-Rho. AIM(S): In the present study, the effects of fear memory consolidation and retrieval on the mRNA expression of Gα from all GP families were assessed in HP, Amy and PFC. METHOD(S): C57BL/6J mice were subject to 1-day fear conditioning (FC) procedure followed by contextual (CTX) or cued (Cs) retrieval test of freezing behavior. Morphine (1mg/kg/ip) injected immediately after FC was used to prevent fear consolidation process. RealTime PCR technique was adopted to measure mRNA expression of Gα subunits: 1 h after FC, 24 h later, 1 h after CTX or Cs retrieval test. RESULTS: In HP, the increased levels of Gα(s), (12) and (11) were observed 1 h after FC. The Gα(s) mRNA decreased (vs. control) when consolidation was stabilized as well after Cs retrieval. Elevated Gα(12) mRNA, as observed 1h after FC, returned to control level at fear memory stabilization and raised again with CTX retrieval. The increase in Gα(11) persisted 24 h after FC and after CTX (but not Cs) retrieval. In PFC, the CTX retrieval was accompanied by a decrease in Gα(i2) and (i3) mRNA levels. In Amy, no specific change to fear memory process was observed. CONCLUSIONS: FC evoked changes in Gα mRNA expression are observed mainly in HP and mostly connected to CTX learning. Results suggest that activated signaling pathways from Gα(s) and Gα(12) are necessary to begin fear memory consolidation process in HP while signal transduction via Gα(11) is implicated in maintenance of fear consolidation. FINANCIAL SUPPORT: Supported by statutory funds from the Institute of Pharmacology PAS.
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Spatial Memory and differentation of adult hippocampal neurons: role of timing

84%
Cestari V., Furioli-Vecchioli S., Saraulli D., Constanzi M., Pacioni S., Cina L., Aceti M., Micheli L., Bacci A., Tirone F.
Acta Neurobiologiae Experimentalis
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2009
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tom 69
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nr 3
In the dentate gyrus adult neurogenesis plays a critical role in hippocampus-dependent spatial learning. However, how new neurons become functionally integrated into spatial circuits and contribute to learning and memory remains yet unknown. To study this issue, we used a mouse model in which the differentiation of adultgenerated dentate gyrus neurons can be anticipated by conditionally expressing the pro-differentiative gene PC3 (Tis21/BTG2) in nestin-positive progenitor cells. This strategy selectively changes the timing of differentiation of newly generated neurons without affecting their number. New, adult-generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation, reduced dendritic arborization and spine density. The genetic manipulation affected different hippocampusdependent learning and memory tasks and selectively reduced synaptic plasticity in the dentate gyrus. Morphological and functional analyses of hippocampal neurons at different stages of differentiation, following transgene activation within defi ned time-windows, revealed that the new, adult-generated neurons up to 3–4 weeks of age are required not only to acquire new spatial information but also to use previously consolidated memories. Thus, the correct unwinding of these key memory functions is critically dependent on the correct timing of the initial stages of neuron maturation and connection to existing circuits.
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