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Theta and gamma frequency oscillations occur in the same brain regions and interact with each other, a process called cross-frequency coupling. Here, we review evidence for the following hypothesis: that the dual oscillations form a code for representing multiple items in an ordered way. This form of coding has been most clearly demonstrated in the hippocampus, where different spatial information is represented in different gamma subcycles of a theta cycle. Other experiments have tested the functional importance of oscillations and their coupling. These involve correlation of oscillatory properties with memory states, correlation with memory performance, and effects of disrupting oscillations on memory. Recent work suggests that this coding scheme coordinates communication between brain regions and is involved in sensory as well as memory processes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Rate remapping is a recently revealed neural code in which sensory information modulates the firing rate of hippocampal place cells. The mechanism underlying rate remapping is unknown. Its characteristic modulation, however, must arise from the interaction of the two major inputs to the hippocampus, the medial entorhinal cortex (MEC), in which grid cells represent the spatial position of the rat, and the lateral entorhinal cortex (LEC), in which cells represent the sensory properties of the environment. We have used computational methods to elucidate the mechanism by which this interaction produces rate remapping. We show that the convergence of LEC and MEC inputs, in conjunction with a competitive network process mediated by feedback inhibition, can account quantitatively for this phenomenon. The same principle accounts for why different place fields of the same cell vary independently as sensory information is altered. Our results show that rate remapping can be explained in terms of known mechanisms., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The pre/post debate involves the question of whether long-term potentiation (LTP) is mediated by enhancement of release, enhancement of postsynaptic receptors, or both. Recent papers have presented evidence for purely postsynaptic or purely presynaptic changes, and a paper by Ahmed and Siegelbam (in this issue of Neuron) suggests a mechanism by which release is enhanced. This debate is increasingly constrained by technical advances that allow central synapses to be studied with increasing precision. A possible of way of reconciling conflicting evidence is suggested.

In this article we develop the concept that the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop. Activation of the loop begins when the hippocampus detects newly arrived information that is not already stored in its long-term memory. The resulting novelty signal is conveyed through the subiculum, accumbens, and ventral pallidum to the VTA where it contributes (along with salience and goal information) to the novelty-dependent firing of these cells. In the upward arm of the loop, dopamine (DA) is released within the hippocampus; this produces an enhancement of LTP and learning. These findings support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is localized in the postsynaptic density (PSD) and is necessary for LTP induction. Much has been learned about the autophosphorylation of CaMKII and its dephosphorylation by PSD protein phosphatase-1 (PP1). Here, we show how the CaMKII/PP1 system could function as an energy-efficient, bistable switch that could be activated during LTP induction and remain active despite protein turnover. We also suggest how recently discovered binding interactions could provide a structural readout mechanism: the autophosphorylated state of CaMKII binds tightly to the NMDAR and forms, through CaMKII-actinin-actin-(4.1/SAP97) linkages, additional sites for anchoring AMPARs at synapses. The proposed model has substantial experimental support and elucidates principles by which a local protein complex could produce stable information storage and readout.

In standard protocols, the frequency of synaptic stimulation determines whether CA1 hippocampal synapses undergo long-term potentiation or depression. Here we show that during cholinergically induced theta oscillation (theta) synaptic plasticity is greatly sensitized and can be induced by a single burst (4 pulses, 100 Hz). A burst given at the peak of theta induces homosynaptic LTP; the same burst at a trough induces homosynaptic LTD of previously potentiated synapses. Heterosynaptic LTD is produced at inactive synapses when others undergo LTP. The synaptic modifications during theta require NMDA receptors and muscarinic receptors. The enhancement is cooperative and occludes with standard LTP. These results suggest that the similar bursts observed during theta rhythm in vivo may be a natural stimulus for inducing LTP/LTD.

We have investigated the role of Ca2+ in the excitation of Limulus photoreceptors by intracellular injection of the Ca2+ buffer, 5,5'-dibromo-BAPTA. Buffer with free Ca2+ of 0.5 or 5 microM slowed the rising edge of the light response over 100-fold and greatly reduced both the transient and plateau phases of the light response, as expected if Ca2+ elevation is necessary for all phases of excitation. Injection of buffers with free Ca2+ of 5 or 45 microM, levels normally reached during light, evoked sustained inward current as expected if Ca2+ is sufficient for excitation. The transduction cascade appears due to a single pathway that sequentially involves 1,4,5-trisphosphate inositol, Ca2+, and cyclic GMP.

Changes in intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons were measured using intracellularly injected fura-2. A large component of the [Ca2+]i elevation caused by high frequency stimulation of the Schaffer collaterals was correlated with the Na+ spikes triggered by the excitatory postsynaptic potentials (EPSPs). These spikes were generated in the soma and proximal dendrites and stimulated Ca2+ entry through voltage-gated Ca2+ channels. Suppressing spikes by hyperpolarizing the soma or by injecting QX-314 revealed a smaller nonspike component of Ca2+ entry. A substantial fraction of this component was mediated by the action of the EPSPs on voltage-gated Ca2+ channels, because it persisted in 2-amino-5-phosphonovaleric acid and because it was usually reduced when Ca2+ channel activity was suppressed by hyperpolarization. Ca2+ entry through the N-methyl-D-aspartate receptor channel could not be detected with certainty, perhaps because it was highly localized.