Young adult-born granule cells (abGCs) in the dentate gyrus (DG) have a profound impact on cognition and mood. However, it remains unclear how abGCs distinctively contribute to local DG information processing. We found that the actions of abGCs in the DG depend on the origin of incoming afferents. In response to lateral entorhinal cortex (LEC) inputs, abGCs exert monosynaptic inhibition of mature granule cells (mGCs) through group II metabotropic glutamate receptors. By contrast, in response to medial entorhinal cortex (MEC) inputs, abGCs directly excite mGCs through N-methyl-D-aspartate receptors. Thus, a critical function of abGCs may be to regulate the relative synaptic strengths of LEC-driven contextual information versus MEC-driven spatial information to shape distinct neural representations in the DG.

Silence of FMR1 causes loss of fragile X mental retardation protein (FMRP) and dysregulated translation at synapses, resulting in the intellectual disability and autistic symptoms of fragile X syndrome (FXS). Synaptic dysfunction hypotheses for how intellectual disabilities like cognitive inflexibility arise in FXS predict impaired neural coding in the absence of FMRP. We tested the prediction by comparing hippocampus place cells in wild-type and FXS-model mice. Experience-driven CA1 synaptic function and synaptic plasticity changes are excessive in Fmr1-null mice, but CA1 place fields are normal. However, Fmr1-null discharge relationships to local field potential oscillations are abnormally weak, stereotyped, and homogeneous; also, discharge coordination within Fmr1-null place cell networks is weaker and less reliable than wild-type. Rather than disruption of single-cell neural codes, these findings point to invariant tuning of single-cell responses and inadequate discharge coordination within neural ensembles as a pathophysiological basis of cognitive inflexibility in FXS. VIDEO ABSTRACT.

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase’s action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1 day to 1 month after training. Therefore, if the mechanisms of PKMζ’s persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1 day to 1 month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase’s action during long-term and remote spatial memory maintenance.

The dentate gyrus (DG) is crucial for behaviorally discriminating similar spatial memories, predicting that DG place cells change ("remap") their relative spatial tuning ("place fields") for memory discrimination. This prediction was never tested, although DG place cells remap across similar environments without memory tasks. We confirm this prior finding but find that DG place fields do not remap across spatial tasks that require DG-dependent memory discrimination. Instead of remapping, place-discriminating discharge is observed transiently among DG place cells, particularly when memory discrimination is most necessary. The DG network may signal memory discrimination by expressing distinctive sub-second network patterns of co-firing at memory discrimination sites. This involves increased coupling of discharge from place cells and interneurons, as was observed during successful, but not failed, behavioral expression of memory discrimination. Instead of remapping, these findings indicate that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.

No abstract

Experimental and theoretical studies demonstrate that neuronal gamma oscillations crucially depend on interneurons, but current models do not consider the diversity of known interneuron subtypes. Moreover, in CA1 of the hippocampus, experimental evidence indicates the presence of multiple gamma oscillators, two of which may be coordinated by differing interneuron populations. In this article, we show that models of networks with competing interneuron populations with different postsynaptic effects are sufficient to generate, within CA1, distinct oscillatory regimes. We find that strong mutual inhibition between the interneuron populations permits distinct fast and slow gamma states, whereas weak mutual inhibition generates mixed gamma states. We develop idealized firing rate models to illuminate dynamic properties of these competitive gamma networks, and reinforce these concepts with basic spiking models. The models make several explicit predictions about gamma oscillators in CA1. Specifically, interneurons of different subtype phase-lock to different gamma states, and one population of interneurons is silenced and the other active during fast and slow gamma events. Finally, mutual inhibition between interneuron populations is necessary to generate distinct gamma states. Previous experimental studies indicate that fast and slow gamma oscillations reflect different information processing modes, although it is unclear whether these rhythms are intrinsic or imposed. The models outlined demonstrate that basic architectures can locally generate these oscillations, as well as capture other features of fast and slow gamma, including theta-phase preference and spontaneous transitions between gamma states. These models may extend to describe general dynamics in networks with diverse interneuron populations. The oscillatory coordination of neural signals is crucial to healthy brain function. We have developed an idealized neuronal model that generates distinct fast and slow gamma oscillations, a known feature of the rodent hippocampus. Our work provides a mechanism of this phenomenon, as well as a theoretical framework for future experiments concerning hippocampal gamma. It moreover offers a tractable model of competitive gamma oscillations that is generalizable across the nervous system.

We have analyzed the yearly averaged sidereal daily variations in the count rates of 46 underground muon telescopes by fitting Gaussian functions to the data. These functions represent the loss cone and tail‐in anisotropies of the sidereal anisotropies model proposed by Nagashima et al. [l995a, b]. The underground muon telescopes cover the median rigidity range 143–1400 GV and the viewing latitude range 73°N–76°S. From the Gaussian amplitudes and positions we have confirmed that the tail‐in anisotropy is more prominent in the southern hemisphere with its reference axis located at declination (δ) ∼14°S and right ascension (α) ∼4.7 sidereal hours. The tail‐in anisotropy is asymmetric about its reference axis, and the observed time of maximum intensity depends on the viewing latitude of the underground muon telescopes. We also find that the declination of the reference axis may be related to the rigidity of the cosmic rays. We show that the loss cone anisotropy is symmetric and has a reference axis located on the celestial equator (δ ∼ 0°) and α ∼ 13 sidereal hours. We have used the parameters of the Gaussian fits to devise an empirical model of the sidereal anisotropies. The model implies that the above characteristics of the anisotropies can explain the observed north‐south asymmetry in the amplitude of the sidereal diurnal variation. Furthermore, we find that the anisotropies should cause the phase of the sidereal semidiurnal variation of cosmic rays to be observed at later times from the northern hemisphere compared to observations from the southern hemisphere. We present these results and discuss them in relation to current models of the heliosphere.

A widely accepted notion for a process underlying memory formation is that learning changes the efficacy of synapses by the mechanism of synaptic plasticity. While there is compelling evidence of changes in synaptic efficacy observed after learning, demonstration of persistent synaptic changes accompanying memory has been elusive. We report that acquisition of a hippocampus and long-term potentiation dependent memory for places persistently changes the function of CA1 synapses. Using extracellular recordings we measured CA3-CA1 and EC-CA1 synaptic responses and found robust changes in the CA3-CA1 pathway after memory training. Crucially, these changes in synaptic function lasted at least a month and coincided with the persistence of long-term place memories; the changes were only observed in animals that expressed robust memory, and not in animals with poor memory recall. Interestingly, our findings were observed at the level of populations of synapses; suggesting that memory formation recruits widespread synaptic circuits and persistently reorganizes their function to store information.