Effect Of GHS-R1a KO On Learning And Memory In Mice And Possible Synaptic Mechanism Analysis

Ghrelin is a 28 amino acid peptide which is secreted by the stomach cells and the hypothalamus. It has a strong effect on promoting growth hormone secretion. Ghrelin exists in plasma by acetylation and deacetylation forms. Acetylating is the main functional form of ghrelin, which can activate ghrelin receptor(GHS-R1a). In the central nervous system(CNS), GHS-R1 a is highly expressed in cortex, hippocampus, amygdala and etc, suggesting possible involvement of the peptide in learning and memory processes.Hippocampus belongs to the limbic system and is composed of four areas: CA1,CA2, CA3 and DG. CA1 and CA3 are the largest and most easily identified sub regions of the hippocampus. The main function of hippocampus is to direct the recent memory.Our previous study showed that ghrelin micro infusion into CA1 during training blocked MWM spatial memory and contextual fear memory. To confirm the effect of ghrelin/GHS-R1 a signaling on memory and explore the underlying synaptic mechanisms,we screened the behavioral phenotype of GHS-R1 a knock-out(KO) mice with a battery of behavioral tests. Meanwhile, we investigated the effect of GHS-R1 a knock-out on synaptic transmission in CA1 of the hippocampus with whole-cell patch clamp technique.Our results were described as following:1. GHS-R1 a KO mice showed normal anxiety and locomotor activity as tested in elevated plus maze and open field.2. GHS-R1 a KO mice showed enhanced spatial memory as tested in Morris water maze.3. GHS-R1 a KO mice showed enhanced contextual fear memory as test 24 h after fear conditioning.4. GHS-R1 a KO increased the frequency of s EPSCs in CA1 pyramidal neurons, but had no effect on amplitude of s EPSCs.5. GHS-R1 a KO increased the frequency but not the amplitude of m EPSCs in CA1 pyramidal neurons.6. GHS-R1 a KO did not change frequency or amplitude of s IPSCs in CA1 pyramidal neurons.7. GHS-R1 a KO increased the frequency of m IPSCs in CA1 pyramidal neurons.In summary, our data showed that GHS-R1 a KO enhanced multiform of memory formation which are hippocampus dependent. The promoting effect may be related to the increased excitatory synaptic transmission and reduced inhibitory synaptic transmission inthe hippocampus network.