| 1. |
- Dickson, C. T., et al.
(författare)
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Properties and role of I-h in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons
- 2000
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 83:5, s. 2562-2579
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Forskningsöversikt (refereegranskat)abstract
- Various subsets of brain neurons express a hyperpolarization-activated inward current (I-h) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na+-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I-h because it was resistant to extracellular Ba2+, sensitive to Cs+, completely and selectively abolished by ZD7288, and carried by both Na+ and K+ ions. I-h in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba2+ gradually and completely abolished the subthreshold oscillations, thus directly implicating I-h in their generation. Using experimentally derived biophysical parameters for I-h and the low-threshold persistent Na+ current (I-NaP) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I-NaP and I-h can sustain persistent subthreshold oscillations in SCs. I-NaP and I-h operate in a push-pull fashion where the delay in the activation/deactivation of I-h gives rise to the oscillatory process.
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| 2. |
- Egorov, A. V., et al.
(författare)
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Graded persistent activity in entorhinal cortex neurons
- 2002
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 420:6912, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time(1,2). Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential(2). Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions(3)-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.
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| 3. |
- Fransén, Erik, 1962-, et al.
(författare)
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Entorhinal neuronal activity during delayed matching tasks may depend upon muscarinic-induced non-specific cation current I(CANM)
- 2001
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Ingår i: Neurocomputing. - 0925-2312 .- 1872-8286. ; 38, s. 601-606
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Tidskriftsartikel (refereegranskat)abstract
- Biophysical compartmental models of stellate, pyramidal-like and interneurons in layer II of the rat entorhinal cortex were used to explore cellular and synaptic components involved in neuronal responses to stimuli in a delayed match to sample (DMS) task. Simulations demonstrate that the muscarinic receptor-induced non-specific cation current, I(CANM), could contribute to these phenomena. Facilitation of I(CANM) by calcium influx during spikes induced by the sample stimulus can cause enhanced responses for matches as well as delay activity. In a network, lateral inhibition can produce match suppression, and in conjunction with stimulus selective/non-selective cells produce non-match enhancement and suppression.
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| 4. |
- Fransén, Erik, 1962-, et al.
(författare)
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Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons
- 2004
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 14:3, s. 368-384
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Tidskriftsartikel (refereegranskat)abstract
- A multi compartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I-NaP) and the hyperpolarization activated inward current (I-h) in the generation of subthreshold membrane potential oscillations. The potential role of I-h in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of I-h and the slow calcium-activated potassium current I-K(AHP) in action potential clustering was also studied. Representations of I-h and I-NaP were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et A, J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of I-h with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of I-h does not follow the fast component down to very short time constants. The model also predicts that the fast component of I-h is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters.
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| 5. |
- Fransén, Erik, 1962-, et al.
(författare)
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Mechanism of graded persistent cellular activity of entorhinal cortex layer V neurons
- 2006
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 49:5, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Working memory is an emergent property of neuronal networks, but its cellular basis remains elusive. Recent data show that principal neurons of the entorhinal cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model provides stable plateau firing generated by a nonspecific calcium-sensitive cationic (CAN) current. Sustained firing is insensitive to small variations in Ca2+ concentration in a neutral zone. However, both high and low Ca2+ levels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high levels of calcium, while decreases in rate occur in the presence of low levels of calcium. The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons.
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| 6. |
- Fransén, Erik, 1962-, et al.
(författare)
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Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM in entorhinal neuronal activity during delayed matching tasks
- 2002
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 22:3, s. 1081-1097
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Tidskriftsartikel (refereegranskat)abstract
- Entorhinal lesions impair performance in delayed matching tasks, and blockade of muscarinic cholinergic receptors also impairs performance in these tasks. Physiological data demonstrate that muscarinic cholinergic receptor stimulation activates intrinsic cellular currents in entorhinal neurons that could underlie the role of entorhinal cortex in performance of these tasks. Here we use a network biophysical simulation of the entorhinal cortex to demonstrate the potential role of this cellular mechanism in the behavioral tasks. Simulations demonstrate how the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM could provide a cellular mechanism for features of the neuronal activity observed during performance of delayed matching tasks. In particular, I-NCM could underlie (1) the maintenance of sustained spiking activity during the delay period, (2) the enhancement of spiking activity during the matching period relative to the sample period, and (3) the resistance of sustained activity to distractors. Simulation of a larger entorhinal network with connectivity chosen randomly within constraints on number, distribution, and weight demonstrates appearance of other phenomena observed in unit recordings from awake animals, including match suppression, non-match enhancement, and non-match suppression.
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| 7. |
- Giocomo, Lisa M., et al.
(författare)
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Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 315:5819, s. 1719-1722
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Tidskriftsartikel (refereegranskat)abstract
- Grid cells in layer II of rat entorhinal cortex fire to spatial locations in a repeating hexagonal grid, with smaller spacing between grid fields for neurons in more dorsal anatomical locations. Data from in vitro whole-cell patch recordings showed differences in frequency of subthreshold membrane potential oscillations in entorhinal neurons that correspond to different positions along the dorsal-to-ventral axis, supporting a model of physiological mechanisms for grid cell responses.
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| 8. |
- Hasselmo, Michael E., et al.
(författare)
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A phase code for memory could arise from circuit mechanisms in entorhinal cortex
- 2009
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Ingår i: Neural Networks. - : PERGAMON-ELSEVIER. - 0893-6080 .- 1879-2782. ; 22:8, s. 1129-1138
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Tidskriftsartikel (refereegranskat)abstract
- Neurophysiological data reveals intrinsic cellular properties that suggest how entorhinal cortical neurons could code memory by the phase of their firing. Potential cellular mechanisms for this phase coding in models of entorhinal function are reviewed. This mechanism for phase coding provides a substrate for modeling the responses of entorhinal grid cells, as well as the replay of neural spiking activity during waking and sleep. Efforts to implement these abstract models in more detailed biophysical compartmental simulations raise specific issues that could be addressed in larger scale population models incorporating mechanisms of inhibition.
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| 9. |
- Hasselmo, M. E., et al.
(författare)
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Computational modeling of entorhinal cortex
- 2000
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Ingår i: PARAHIPPOCAMPAL REGION. - NEW YORK : New York Academy of Sciences. - 1573312630 ; , s. 418-446
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Konferensbidrag (refereegranskat)abstract
- Computational modeling provides a means for linking the physiological and anatomical characteristics of entorhinal cortex at a cellular level to the functional role of this region in behavior. We have developed detailed simulations of entorhinal cortical neurons and networks, with an emphasis on the role of acetylcholine in entorhinal cortical function. Computational modeling suggests that when acetylcholine levels are high, this sets appropriate dynamics for the storage of stimuli during performance of delayed matching tasks. In particular, acetylcholine activates a calcium-sensitive nonspecific cation current which provides an intrinsic cellular mechanism which could maintain neuronal activity across a delay period. Simulations demonstrate how this phenomena could underlie entorhinal cortex delay activity as described in previous unit recordings. Acetylcholine also induces theta rhythm oscillations which may be appropriate for timing of afferent input to be encoded in hippocampus and for extraction of individual stored sequences from multiple stored sequences. Lower levels of acetylcholine may allow sharp wave dynamics which can reactivate associations encoded in hippocampus and drive the formation of additional traces in hippocampus and entorhinal cortex during consolidation.
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