441 research outputs found
Clique topology reveals intrinsic geometric structure in neural correlations
Detecting meaningful structure in neural activity and connectivity data is
challenging in the presence of hidden nonlinearities, where traditional
eigenvalue-based methods may be misleading. We introduce a novel approach to
matrix analysis, called clique topology, that extracts features of the data
invariant under nonlinear monotone transformations. These features can be used
to detect both random and geometric structure, and depend only on the relative
ordering of matrix entries. We then analyzed the activity of pyramidal neurons
in rat hippocampus, recorded while the animal was exploring a two-dimensional
environment, and confirmed that our method is able to detect geometric
organization using only the intrinsic pattern of neural correlations.
Remarkably, we found similar results during non-spatial behaviors such as wheel
running and REM sleep. This suggests that the geometric structure of
correlations is shaped by the underlying hippocampal circuits, and is not
merely a consequence of position coding. We propose that clique topology is a
powerful new tool for matrix analysis in biological settings, where the
relationship of observed quantities to more meaningful variables is often
nonlinear and unknown.Comment: 29 pages, 4 figures, 13 supplementary figures (last two authors
contributed equally
Understanding short-timescale neuronal firing sequences via bias matrices
The brain generates persistent neuronal firing sequences across varying timescales. The short-timescale (~100ms) sequences are believed to be crucial in the formation and transfer of memories. Large-amplitude local field potentials known as sharp-wave ripples (SWRs) occur irregularly in hippocampus when an animal has minimal interaction with its environment, such as during resting, immobility, or slow-wave sleep. SWRs have been long hypothesized to play a critical role in transferring memories from the hippocampus to the neocortex [1]. While sequential firing during SWRs is known to be biased by the previous experiences of the animal, the exact relationship of the short-timescale sequences during SWRs and longer-timescale sequences during spatial and nonspatial behaviors is still poorly understood. One hypothesis is that the sequences during SWRs are âreplaysâ or âpreplaysâ of âmaster sequencesâ, which are sequences that closely mimic the order of place fields on a linear track [2,3]. Rather than particular hard-coded âmasterâ sequences, an alternative explanation of the observed correlations is that similar sequences arise naturally from the intrinsic biases of firing between pairs of cells. To distinguish these and other possibilities, one needs mathematical tools beyond the center-of-mass sequences and Spearmanâs rank-correlation coefficient that are currently used
Memory:Forget me not
An enzyme called PKM zeta may have a role in long-term memory after all
Theta-mediated dynamics of spatial information in hippocampus.
In rodent hippocampus, neuronal activity is organized by a 6-10 Hz theta oscillation. The spike timing of hippocampal pyramidal cells with respect to the theta rhythm correlates with an animal's position in space. This correlation has been suggested to indicate an explicit temporal code for position. Alternatively, it may be interpreted as a byproduct of theta-dependent dynamics of spatial information flow in hippocampus. Here we show that place cell activity on different phases of theta reflects positions shifted into the future or past along the animal's trajectory in a two-dimensional environment. The phases encoding future and past positions are consistent across recorded CA1 place cells, indicating a coherent representation at the network level. Consistent theta-dependent time offsets are not simply a consequence of phase-position correlation (phase precession), because they are no longer seen after data randomization that preserves the phase-position relationship. The scale of these time offsets, 100-300 ms, is similar to the latencies of hippocampal activity after sensory input and before motor output, suggesting that offset activity may maintain coherent brain activity in the face of information processing delays
Place fields and the cognitive map
The discovery of place cells by John O'Keefe in the early 1970s was a breakthrough not just for systems neuroscience, but also for psychology: place fields provided a clear neural substrate for the notion of a cognitive map, a construct devised to explain rat learning and spatial cognition. However, is the robust location-related firing of place cells still best conceptualised as a cognitive map? In this commentary, we reassess this view of hippocampus function in light of subsequent findings on place cells. We argue that as place fields encode local space, and as they are modulated by ongoing behavior, the representation they provide may be more cognitive than map-like
Complexity without chaos: Plasticity within random recurrent networks generates robust timing and motor control
It is widely accepted that the complex dynamics characteristic of recurrent
neural circuits contributes in a fundamental manner to brain function. Progress
has been slow in understanding and exploiting the computational power of
recurrent dynamics for two main reasons: nonlinear recurrent networks often
exhibit chaotic behavior and most known learning rules do not work in robust
fashion in recurrent networks. Here we address both these problems by
demonstrating how random recurrent networks (RRN) that initially exhibit
chaotic dynamics can be tuned through a supervised learning rule to generate
locally stable neural patterns of activity that are both complex and robust to
noise. The outcome is a novel neural network regime that exhibits both
transiently stable and chaotic trajectories. We further show that the recurrent
learning rule dramatically increases the ability of RRNs to generate complex
spatiotemporal motor patterns, and accounts for recent experimental data
showing a decrease in neural variability in response to stimulus onset
Coordinated grid and place cell replay during rest
Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex
Zeta Inhibitory Peptide attenuates learning and memory by inducing NO-mediated downregulation of AMPA receptors
Zeta inhibitory peptide (ZIP), a PKMζ inhibitor, is widely used to interfere with the main- tenance of acquired memories. ZIP is able to erase memory even in the absence of PKMζ, via an unknown mechanism. We found that ZIP induces redistribution of the AMPARGluA1 in HEK293 cells and primary cortical neurons, and decreases AMPAR-mediated currents in the nucleus accumbens (NAc). These effects were mimicked by free arginine or by a modified ZIP in which all but the arginine residues were replaced by alanine. Redistribution was blocked by a peptidase-resistant version of ZIP and by treatment with the nitric oxide (NO)- synthase inhibitor L-NAME. ZIP increased GluA1-S831 phosphorylation and ZIP-induced redistribution was blocked by nitrosyl-mutant GluA1-C875S or serine-mutant GluA1-S831A. Introducing the cleavable arginine-alanine peptide into the NAc attenuated expression of cocaine-conditioned reward. Together, these results suggest that ZIP may act as an arginine donor, facilitating NO-dependent downregulation of AMPARs, thereby attenuating learning and memory
Erasing Sensorimotor Memories via PKMζ Inhibition
Sensorimotor cortex has a role in procedural learning. Previous studies suggested that this learning is subserved by long-term potentiation (LTP), which is in turn maintained by the persistently active kinase, protein kinase Mzeta (PKMζ). Whereas the role of PKMζ in animal models of declarative knowledge is established, its effect on procedural knowledge is not well understood. Here we show that PKMζ inhibition, via injection of zeta inhibitory peptide (ZIP) into the rat sensorimotor cortex, disrupts sensorimotor memories for a skilled reaching task even after several weeks of training. The rate of relearning the task after the memory disruption by ZIP was indistinguishable from the rate of initial learning, suggesting no significant savings after the memory loss. These results indicate a shared molecular mechanism of storage for declarative and procedural forms of memory
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