Representing information in cell assemblies: Persistent activity mediated by semilunar granule cells

Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, USA.
Nature Neuroscience (Impact Factor: 14.98). 02/2010; 13(2):213-22. DOI: 10.1038/nn.2458
Source: PubMed

ABSTRACT Here we found that perforant path stimulation in rat hippocampal slices evoked long-lasting barrages of synaptic inputs in subpopulations of dentate gyrus mossy cells and hilar interneurons. Synaptic barrages triggered persistent firing in hilar neurons (hilar up-states). We found that synaptic barrages originate from semilunar granule cells (SGCs), glutamatergic neurons in the inner molecular layer that generate long-duration plateau potentials in response to excitatory synaptic input. MK801, nimodipine and nickel all abolished both stimulus-evoked plateau potentials in SGCs and synaptic barrages in downstream hilar neurons without blocking fast synaptic transmission. Hilar up-states triggered functional inhibition in granule cells that persisted for more than 10 s. Hilar cell assemblies, identified by simultaneous triple and paired intracellular recordings, were linked by persistent firing in SGCs. Population responses recorded in hilar neurons accurately encoded stimulus identity. Stimulus-evoked up-states in the dentate gyrus represent a potential cellular basis for hippocampal working memory.

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    • "However , the intrinsic properties of neurons are not always ''ideal.'' For example, semilunar granule cells in the dentate gyrus can fire APs for a long duration in response to brief stimulation of the perforant pathway (Larimer and Strowbridge, 2010), and neocortical pyramidal cells (PCs) can generate graded persistent activity while metabotropic receptors are activated (Egorov et al., 2002; Sidiropoulou et al., 2009). Despite the lack of substantial evidence for the behavioral relevance of ''unideal'' neurons , theoretical studies have suggested important roles of these neurons in cortical functions (Lisman et al., 1998; Loewenstein and Sompolinsky, 2003). "
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    ABSTRACT: A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs) but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na(+) current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 03/2015; 9(9). DOI:10.1016/j.celrep.2015.02.018 · 8.36 Impact Factor
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    • "Transient stimulation of the rodent perforant path has also been shown to induce persistent firing of dentate gyrus granule cells, leading to up-states of mossy fibers and subsequent hilar neurons. It is thought that persistent activity in assemblies of hilar neurons may help generate short-term memory representations of stimulus features, such as during stimulus novelty (Larimer and Strowbridge, 2009). The combination of high-resolution DTI of white matter pathways and novel techniques of electrode visualization combined with simultaneous DBS, imaging and electrophysiological recordings will aid in determining the precise location of DBS electrodes that will produce the largest neuroenhancing of effects on hippocampal-dependent memory. "
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    ABSTRACT: Episodic memory, or the ability to remember personal experienced events, is severely compromised in various neurological disorders affecting the medial temporal lobe (MTL) including Alzheimer's disease, temporal lobe epilepsy, traumatic brain injury and other MTL injuries such as those occurring during stroke, cardiac arrest, or encephalitis. While deep brain stimulation (DBS) has been used to successfully treat movement disorders such as Parkinson's disease and dystonia, an exciting new frontier of DBS is the enhancement of cognitive function, and memory in particular. The implications of such enhancement to patients affected with disorders of memory may be of great significance. In the current review, we summarize several studies illustrating the potential for DBS or cortical surface stimulation to enhance episodic learning and memory. We also discuss and propose several future directions that would provide necessary insight as to whether DBS could be useful for treating memory disorders.
    NeuroImage 08/2013; 85. DOI:10.1016/j.neuroimage.2013.07.066 · 6.36 Impact Factor
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    • "Alternatively, Williams et al. (2007) recently found that although spiny, granule-like neurons in the inner molecular layer (IML), termed " semilunar granule cells, " project to granule cells, these cells' axon collaterals mono-synaptically excite mossy cells. Since semilunar granule cells receive the input from entorhinal cortex in the molecular layer, it is suggested that semilunar granule cells may provide an alternate pathway for entorhinal inputs to persistently drive hilar neurons and CA3 cells (Larimer and Strowbridge, 2010; Gupta et al., 2012). Interestingly, semilunar granule cells also appear to receive mono-synaptic excitatory input from mossy cells (Williams et al., 2007), potentially making " reverberatory circuits. "
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    ABSTRACT: Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability-the "dormant basket cell" and the "irritable mossy cell" hypotheses. The "dormant basket cell" hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The "irritable mossy cell" hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.
    Frontiers in Neural Circuits 02/2013; 7:14. DOI:10.3389/fncir.2013.00014 · 2.95 Impact Factor
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