Four projects are proposed to investigate neuronal properties and circuit properties that give rise to various physiological phenomena seen in the hippocampus that are thought to be related to its role in learning and memory. The projects are described within the context of an overall effort to investigate 'frequency' vs. 'temporal coding' approaches to understanding representation and information processing in the hippocampus. The first project will analyze the timing of neuronal activation in three classes of neurons (pyramidal cells, stratum oriens interneurons, pyramidal-layer interneurons) in three different hippocampal states (theta, sharp-wave, and no-sharp wave). The results will constrain developing conceptualizations of how the pattern of overall activation seen in each state arises and how individual neurons contribute to and/or reflect these processes. The second project consists of four experiments concerning place cells. A 'space clamp' procedure is used in which an animal is placed at a location in a maze in a running wheel. This allows stable recording of a place cell while the animal is fixed in place; multiple places can be tested. Experiment 1 asks if phase advancement correlates with increase in firing rate induced by increasing the animals running rate. Experiment 2 asks if monosynaptically coupled pyramidal cell/interneuron pairs both exhibit place cell advancement. Experiment 3 asks if place cells can be artificially induced by stimulating them at the same time a natural place cell fires, thereby inducing them to learn to respond to (a subset of) the inputs that are firing the natural place cell. Experiment 4 tests the hypothesis that an experimentally induced spike in a pyramidal cell can induce a monosynaptic spike in a neighboring interneuron. The third project considers whether spikes can be initiated in dendrites of hippocampal pyramidal cells in vivo. Dual dendritic (IC) /somatic (EC) recordings are used. The first experiment will attempt to discover whether and under what circumstances spikes appear first in dendrites and then propagate to the cell body. The second will attempt to show that some dendritic spikes are not accompanied by spikes at the cell body. The third experiment will pair evoked dendritic spikes with commisural stimulation to create inhibition, to see if this tends to prevent the dendritic spike from reaching the soma. The fourth project is to determine the parameters that allow reliable separation of pyramidal cells and interneurons. It is already possible to separate int(p) and p, but int(a/o) are harder. They may be separable we are told using width of the spike at base. The second experiment will use simultaneous ic and ec recording to determine how reliably spikes detected by ic are also detected be ec. This is important as a control esp for the experiments in project 3, where ec is used to determine whether a dendritic spike has reached the soma. EC neurons with large, medium and small spike amplitudes will be studied to see just how reliably individual neuron's spikes are being detected by current methods that depend on cluster cutting. The results will be used to moderate conclusions based on EC data if reliability is low. Misses and FA's will be considered.
| Oliva, Azahara; Fernández-Ruiz, Antonio; Fermino de Oliveira, Eliezyer et al. (2018) Origin of Gamma Frequency Power during Hippocampal Sharp-Wave Ripples. Cell Rep 25:1693-1700.e4 |
| Levenstein, Daniel; Watson, Brendon O; Rinzel, John et al. (2017) Sleep regulation of the distribution of cortical firing rates. Curr Opin Neurobiol 44:34-42 |
| Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gerg? A et al. (2017) Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling. Neuron 93:1213-1226.e5 |
| Peyrache, Adrien; Schieferstein, Natalie; Buzsáki, Gyorgy (2017) Transformation of the head-direction signal into a spatial code. Nat Commun 8:1752 |
| Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas et al. (2015) NeuroGrid: recording action potentials from the surface of the brain. Nat Neurosci 18:310-5 |
| Roux, Lisa; Buzsáki, György (2015) Tasks for inhibitory interneurons in intact brain circuits. Neuropharmacology 88:10-23 |
| Peyrache, Adrien; Lacroix, Marie M; Petersen, Peter C et al. (2015) Internally organized mechanisms of the head direction sense. Nat Neurosci 18:569-75 |
| Buzsáki, György; Stark, Eran; Berényi, Antal et al. (2015) Tools for probing local circuits: high-density silicon probes combined with optogenetics. Neuron 86:92-105 |
| Watson, Brendon O; Buzsáki, György (2015) Sleep, Memory & Brain Rhythms. Daedalus 144:67-82 |
| Agarwal, Gautam; Stevenson, Ian H; Berényi, Antal et al. (2014) Spatially distributed local fields in the hippocampus encode rat position. Science 344:626-30 |
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