CACNA1A-associated epilepsy and ataxia frequently accompany cognitive impairments as devastating co-morbidities. However, it is unclear whether the cognitive deficits are consequences secondary to the neurological symptoms elicited by CACNA1A mutations. To address this issue, Cacna1a mutant mice tottering (tg), and in particular tg/+ heterozygotes, serve as a suitable model system, given that tg/+ heterozygotes fail to display spontaneous absence epilepsy and ataxia typically observed in tg/tg homozygotes. Here, we examined hippocampus-dependent behaviors and hippocampal learning-related synaptic plasticity in tg mice. In behavioral analyses of tg/+ and tg/tg, acquisition and retention of spatial reference memory were characteristically impaired in the Morris water maze task, while working memory was intact in the eight-arm radial maze and T-maze tasks. tg/+ heterozygotes showed normal motor function in contrast to tg/tg homozygotes. In electrophysiological analyses, Schaffer collateral-CA1 synapses showed a deficit in the maintenance of long-term potentiation in tg/+ and tg/tg mice and an increased paired-pulse facilitation induced by paired pulses with 100 ms in tg/tg mice. Our results indicate that the tg mutation causes a dominant disorder of the hippocampus-related memory and synaptic plasticity, raising the possibility that in CACNA1A-associated human diseases, functionally aberrant CaV2.1 Ca2+ channels actively induce the observed cognitive deficits independently of the neurological symptoms.