Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life. In the mammalian hippocampus, a region important for spatial and episodic memory, thousands of new granule cells are produced per day, with the exact number depending on environmental conditions and physical exercise. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories.

Neurons in the medial entorhinal cortex exhibit a grid-like spatial pattern of spike rates that has been proposed to represent a neural code for path integration. To understand how grid cell firing arises from the combination of intrinsic conductances and synaptic input in medial entorhinal stellate cells, we performed patch-clamp recordings in mice navigating in a virtual-reality environment. We found that the membrane potential signature of stellate cells during firing field crossings consisted of a slow depolarization driving spike output. This was best predicted by network models in which neurons receive sustained depolarizing synaptic input during a field crossing, such as continuous attractor network models of grid cell firing. Another key feature of the data, phase precession of intracellular theta oscillations and spiking with respect to extracellular theta oscillations, was best captured by an oscillatory interference model. Thus, these findings provide crucial new information for a quantitative understanding of the cellular basis of spatial navigation in the entorhinal cortex.

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Although dendritic signal processing has been extensively investigated in hippocampal pyramidal cells, only little is known about dendritic integration of synaptic potentials in dentate gyrus granule cells, the first stage in the hippocampal trisynaptic circuit. Here we combined dual whole-cell patch-clamp recordings with high-resolution two-photon microscopy to obtain detailed passive cable models of hippocampal granule cells from adult mice. Passive cable properties were determined by direct fitting of the compartmental model to the experimentally measured voltage responses to short and long current pulses. The data are best fit by a cable model with homogenously distributed parameters, including an average specific membrane resistance (R m ) of 38.0 k⍀ cm 2 , a membrane capacitance (C m ) of 1.0 F cm Ϫ2, and an intracellular resistivity (R i ) of 194 ⍀ cm. Computational analysis shows that signal propagation from somata into dendrites is more efficient in granule cells compared with CA1 pyramidal cells for both steady-state and sinusoidal voltage waveforms up to the gamma frequency range ( f 50% of 74 Hz). Similarly, distal synaptic inputs from entorhinal fibers can efficiently depolarize the somatic membrane of granule cells. Furthermore, the time course of distal dendritic synaptic potentials is remarkably fast, and temporal summation is restricted to a narrow time window in the range of ϳ10 ms attributable to the rapid dendritic charge redistribution during transient voltage signals. Therefore, the structure of the granule cell dendritic tree may be critically important for precise dendritic signal processing and coincidence detection during hippocampus-dependent memory formation and retrieval.