Abstract
BackgroundDendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.ResultsWe have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.ConclusionsThese results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus.
Highlights
Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain
We found that Kal7KO mice exhibit normal AMPA receptor-mediated basal transmission, profound deficits in NMDA receptordependent long-term potentiation (LTP) and long-term depression (LTD), and normal NMDA receptor-independent plasticity
Kal7KO mice exhibit deficits in NMDA receptor-dependent plasticity In addition to regulating spine number, Kal7 interacts with other postsynaptic density proteins involved in synaptic function, and has been suggested to play a key role in activity-dependent plasticity [23,24,25]
Summary
Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. An abundance of research in the field of synaptic plasticity has demonstrated that dendritic spines display morphological plasticity in response to a myriad of extracellular stimuli [1,2]. These changes are thought to be cellular correlates of the plasticity seen in learning and memory [3]. The ability of dendritic spines to remain labile/plastic is dependent on rearrangement of the actin cytoskeleton which forms the core of each spine [10,11,12]. This process is dependent on the activity of Rho-GTPases, which
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