The dominant theoretical form of mental structure of the last century was implicitly a neuropsychological model. At the center of this model, necessary for episodic free recall, planning or logical reasoning, is Hebb's phase sequences of neuronal assemblies, i.e., hypothetical self- propagating loops of neuronal coalitions connected by modifiable synapses. These phase sequences can be activated by exogenous or endogenous (internal) sources of stimulation, allowing the mind a degree of independence from environmental determinants of behavior. The neurophysiological implication of this conjecture for episodic recall is that hippocampal networks are endowed by an internal mechanism that can generate a perpetually changing neuronal activity even in the absence of environmental inputs. Recall of similar episodes would generate similar cell assembly sequences, and uniquely different sequence patterns would reflect different episodes. Recent advances in large-scale recording of neuronal ensembles in the behaving animal have allowed testing this hypothesis. Accordingly, we propose to examine the presence of cell assembly sequences in the hippocampus and entorhinal cortex as a potential substrate of memory recall and/or action planning using a hippocampus-dependent delayed alternation task. To achieve this goal, the experimental animal, rat, will be required to run steadily in a wheel during the delay so that environmental and bodily cues will be kept constant. Our pilot experiments indicate that under these conditions continuously changing cell assemblies form unique sequences specific to the future choice by the rat in the maze. In the first project, traditionally accepted parameters of `place'and `grid'cells during spatial behavior (e.g., `life time'of activity, relation to theta oscillation phase, `temporal compression') will be compared to parameters obtained during wheel running. Experiments in the second project, will examine the conditions (e.g., context, length of experience) that are responsible for establishing the memory specific, unique cell sequence patterns. In the last project, the cell assembly dynamics will be perturbed to examine the causal link between neuronal activity and behavior. The experiments of this proposal will provide an important step towards understanding how emergent, coordinated properties of assembly activity represent cognitive behavior. Dysfunction of self-organized cellular-synaptic mechanisms may underline Alzheimer's disease, schizophrenia and other cognitive diseases.
Using large-scale recording of neuronal activity in the rat, we will examine the hypothesis that self-organized sequences of neuronal assemblies in the hippocampus underlie memory recall and/or planning. Similar internally generated cell assembly sequences may be responsible for several other cognitive functions, including planning and logical reasoning. Dysfunction of self-organized cellular-synaptic mechanisms may underline Alzheimer's disease, schizophrenia and other cognitive diseases.
|Peyrache, Adrien; Lacroix, Marie M; Petersen, Peter C et al. (2015) Internally organized mechanisms of the head direction sense. Nat Neurosci 18:569-75|
|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|
|Watson, Brendon O; BuzsÃ¡ki, GyÃ¶rgy (2015) Sleep, Memory & Brain Rhythms. Daedalus 144:67-82|
|BuzsÃ¡ki, GyÃ¶rgy; Stark, Eran; BerÃ©nyi, Antal et al. (2015) Tools for probing local circuits: high-density silicon probes combined with optogenetics. Neuron 86:92-105|
|Roux, Lisa; BuzsÃ¡ki, GyÃ¶rgy (2015) Tasks for inhibitory interneurons in intact brain circuits. Neuropharmacology 88:10-23|
|Sullivan, David; Mizuseki, Kenji; Sorgi, Anthony et al. (2014) Comparison of sleep spindles and theta oscillations in the hippocampus. J Neurosci 34:662-74|
|Gorgun, Falih Murat; Zhuo, Ming; Singh, Shilpee et al. (2014) Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain. Inhal Toxicol 26:361-9|
|English, Daniel F; Peyrache, Adrien; Stark, Eran et al. (2014) Excitation and inhibition compete to control spiking during hippocampal ripples: intracellular study in behaving mice. J Neurosci 34:16509-17|
|Mizuseki, Kenji; Buzsaki, Gyorgy (2014) Theta oscillations decrease spike synchrony in the hippocampus and entorhinal cortex. Philos Trans R Soc Lond B Biol Sci 369:20120530|
|Stark, Eran; Roux, Lisa; Eichler, Ronny et al. (2014) Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations. Neuron 83:467-80|
Showing the most recent 10 out of 124 publications