Abstract
Cognitive ability and the properties of brain oscillation are highly heritable in humans. Genetic variation underlying oscillatory activity might give rise to differences in cognition and behavior. How genetic diversity translates into altered properties of oscillations and synchronization of neuronal activity is unknown. To address this issue, we investigated cellular and synaptic mechanisms of hippocampal fast network oscillations in eight genetically distinct inbred mouse strains. The frequency of carbachol-induced oscillations differed substantially between mouse strains. Since GABAergic inhibition sets oscillation frequency, we studied the properties of inhibitory synaptic inputs (IPSCs) received by CA3 and CA1 pyramidal cells of three mouse strains that showed the highest, lowest and intermediate frequencies of oscillations. In CA3 pyramidal cells, the frequency of rhythmic IPSC input showed the same strain differences as the frequency of field oscillations. Furthermore, IPSC decay times in both CA1 and CA3 pyramidal cells were faster in mouse strains with higher oscillation frequencies than in mouse strains with lower oscillation frequency, suggesting that differences in GABAA-receptor subunit composition exist between these strains. Indeed, gene expression of GABAA-receptor β2 (Gabrb2) and β3 (Gabrb2) subunits was higher in mouse strains with faster decay kinetics compared with mouse strains with slower decay kinetics. Hippocampal pyramidal neurons in mouse strains with higher oscillation frequencies and faster decay kinetics fired action potential at higher frequencies. These data indicate that differences in genetic background may result in different GABAA-receptor subunit expression, which affects the rhythm of pyramidal neuron firing and fast network activity through GABA synapse kinetics.
Highlights
Variation in cognitive abilities in humans can for a large part be explained by genetic variation
Recently, we reported that in eight genetically different inbred mouse strains variation in properties of fast hippocampal network oscillations can be partly explained by genetic differences (Jansen et al, 2009). To test whether these genetic differences are reflected in properties of excitatory and inhibitory synapses in CA3 and CA1, which underlie fast network oscillations in these areas (Whittington et al, 1995; Mann et al, 2005) and information transfer between these areas, we recorded synaptic activity in CA1 and CA3 pyramidal neurons during fast network oscillations
Since GABAergic synaptic properties and IPSC kinetics can strongly affect the frequency of fast network oscillations, we investigated whether differences exist in GABAergic synaptic transmission received by CA3 pyramidal neurons of NOD and Balbc mice
Summary
Variation in cognitive abilities in humans can for a large part be explained by genetic variation. Twin studies have shown that in humans properties of brain oscillations are highly heritable (Posthuma et al, 2001b; Smit et al, 2005; Linkenkaer-Hansen et al, 2007). Findings in laboratory animals show that gamma-band oscillations in the hippocampus are most likely involved in memory encoding and retrieval (Lisman and Idiart, 1995; Montgomery and Buzsaki, 2007). Phase coupling of gamma oscillations between CA1 and CA3 increases during memory retrieval (Montgomery and Buzsaki, 2007), which occurs at different gamma frequencies than between CA1 and the enthorinal cortex (Colgin et al, 2009). Genetic variation resulting in differences in brain oscillations may give rise to differences in cognition and intelligence in general. How genetic differences translate into differences in properties of oscillations and synchronization of neuronal activity is poorly understood
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