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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References
Schiller, J., Major, G., Koester, H.J. & Schiller, Y. NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature 404, 285–289 (2000).
Sanchez-Vives, M.V. & McCormick, D.A. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat. Neurosci. 3, 1027–1034 (2000).
Egorov, A.V., Hamam, B.N., Fransén, E., Hasselmo, M.E. & Alonso, A.A. Graded persistent activity in entorhinal cortex neurons. Nature 420, 173–178 (2002).
Colombo, M. & Gross, C.G. Responses of inferior temporal cortex and hippocampal neurons during delayed matching to sample in monkeys (Macaca fascicularis). Behav. Neurosci. 108, 443–455 (1994).
Fraser, D.D. & MacVicar, B.A. Cholinergic-dependent plateau potential in hippocampal CA1 pyramidal neurons. J. Neurosci. 16, 4113–4128 (1996).
Funahashi, S., Bruce, C.J. & Goldman-Rakic, P.S. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J. Neurophysiol. 61, 331–349 (1989).
Funahashi, S., Chafee, M.V. & Goldman-Rakic, P.S. Prefrontal neuronal activity in rhesus monkeys performing a delayed anti-saccade task. Nature 365, 753–756 (1993).
Hampson, R.E., Simeral, J.D. & Deadwyler, S.A. Keeping on track: firing of hippocampal neurons during delayed-nonmatch-to-sample performance. J. Neurosci. 22, RC198 (2002).
Major, G. & Tank, D. Persistent neural activity: prevalence and mechanisms. Curr. Opin. Neurobiol. 14, 675–684 (2004).
Aksay, E., Gamkrelidze, G., Seung, H.S., Baker, R. & Tank, D.W. In vivo intracellular recording and perturbation of persistent activity in a neural integrator. Nat. Neurosci. 4, 184–193 (2001).
McCormick, D.A., Connors, B.W., Lighthall, J.W. & Prince, D.A. Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J. Neurophysiol. 54, 782–806 (1985).
Spruston, N. & Johnston, D. Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons. J. Neurophysiol. 67, 508–529 (1992).
Hebb, D. The Organization of Behavior (John Wiley & Sons: New York, 1949).
Seung, H.S. How the brain keeps the eyes still. Proc. Natl. Acad. Sci. USA 93, 13339–13344 (1996).
Abeles, M. et al. Cortical activity flips among quasi-stationary states. Proc. Natl. Acad. Sci. USA 92, 8616–8620 (1995).
Amit, D.J. & Mongillo, G. Spike-driven synaptic dynamics generating working memory states. Neural Comput. 15, 565–596 (2003).
Goldman, M.S., Levine, J.H., Major, G., Tank, D.W. & Seung, H.S. Robust persistent neural activity in a model integrator with multiple hysteretic dendrites per neuron. Cereb. Cortex 13, 1185–1195 (2003).
Seung, H.S., Lee, D.D., Reis, B.Y. & Tank, D.W. Stability of the memory of eye position in a recurrent network of conductance-based model neurons. Neuron 26, 259–271 (2000).
Williams, P.A., Larimer, P., Gao, Y. & Strowbridge, B.W. Semilunar granule cells: glutamatergic neurons in the rat dentate gyrus with axon collaterals in the inner molecular layer. J. Neurosci. 27, 13756–13761 (2007).
Strowbridge, B.W., Buckmaster, P.S. & Schwartzkroin, P.A. Potentiation of spontaneous synaptic activity in rat mossy cells. Neurosci. Lett. 142, 205–210 (1992).
Scharfman, H.E. Characteristics of spontaneous and evoked EPSPs recorded from dentate spiny hilar cells in rat hippocampal slices. J. Neurophysiol. 70, 742–757 (1993).
Strowbridge, B.W. & Schwartzkroin, P.A. Transient potentiation of spontaneous EPSPs in rat mossy cells induced by depolarization of a single neurone. J. Physiol. (Lond.) 494, 493–510 (1996).
Cheng, S. & Frank, L.M. New experiences enhance coordinated neural activity in the hippocampus. Neuron 57, 303–313 (2008).
Soriano, E. & Frotscher, M. Mossy cells of the rat fascia dentata are glutamate-immunoreactive. Hippocampus 4, 65–69 (1994).
Scharfman, H.E. Electrophysiological evidence that dentate hilar mossy cells are excitatory and innervate both granule cells and interneurons. J. Neurophysiol. 74, 179–194 (1995).
Buckmaster, P.S., Wenzel, H.J., Kunkel, D.D. & Schwartzkroin, P.A. Axon arbors and synaptic connections of hippocampal mossy cells in the rat in vivo. J. Comp. Neurol. 366, 271–292 (1996).
Larimer, P. & Strowbridge, B.W. Nonrandom local circuits in the dentate gyrus. J. Neurosci. 28, 12212–12223 (2008).
Mayer, M.L. & Westbrook, G.L. Permeation and block of N-methyl-d-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J. Physiol. (Lond.) 394, 501–527 (1987).
Xu, W. & Lipscombe, D. Neuronal Ca(V)1.3α(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J. Neurosci. 21, 5944–5951 (2001).
Fox, A.P., Nowycky, M.C. & Tsien, R.W. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J. Physiol. (Lond.) 394, 149–172 (1987).
Chow, K.Y., Wu, C., Sui, G.P. & Fry, C.H. Role of the T-type Ca2+ current on the contractile performance of guinea pig detrusor smooth muscle. Neurourol. Urodyn. 22, 77–82 (2003).
Georgopoulos, A.P., Schwartz, A.B. & Kettner, R.E. Neuronal population coding of movement direction. Science 233, 1416–1419 (1986).
Miller, L.M. & Recanzone, G.H. Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity. Proc. Natl. Acad. Sci. USA 106, 5931–5935 (2009).
MacLean, J.N., Watson, B.O., Aaron, G.B. & Yuste, R. Internal dynamics determine the cortical response to thalamic stimulation. Neuron 48, 811–823 (2005).
Acsády, L., Kamondi, A., Sík, A., Freund, T. & Buzsáki, G. GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J. Neurosci. 18, 3386–3403 (1998).
Scharfman, H.E. Dentate hilar cells with dendrites in the molecular layer have lower thresholds for synaptic activation by perforant path than granule cells. J. Neurosci. 11, 1660–1673 (1991).
Ishizuka, N., Weber, J. & Amaral, D.G. Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat. J. Comp. Neurol. 295, 580–623 (1990).
Scharfman, H.E. Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells. J. Neurophysiol. 72, 2167–2180 (1994).
Jefferys, J.G. Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol. Rev. 75, 689–723 (1995).
Williams, S.R., Tóth, T.I., Turner, J.P., Hughes, S.W. & Crunelli, V. The 'window' component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neurones. J. Physiol. (Lond.) 505, 689–705 (1997).
Wei, D.S. et al. Compartmentalized and binary behavior of terminal dendrites in hippocampal pyramidal neurons. Science 293, 2272–2275 (2001).
Hughes, S.W., Cope, D.W., Tóth, T.I., Williams, S.R. & Crunelli, V. All thalamocortical neurones possess a T-type Ca2+ 'window' current that enables the expression of bistability-mediated activities. J. Physiol. (Lond.) 517, 805–815 (1999).
Lo, F.S. & Erzurumlu, R.S. L-type calcium channel-mediated plateau potentials in barrelette cells during structural plasticity. J. Neurophysiol. 88, 794–801 (2002).
Koschak, A. et al. Molecular nature of anomalous L-type calcium channels in mouse cerebellar granule cells. J. Neurosci. 27, 3855–3863 (2007).
Talley, E.M. et al. Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J. Neurosci. 19, 1895–1911 (1999).
Marr, D. Simple memory: a theory for archicortex. Phil. Trans. R. Soc. Lond. B 262, 23–81 (1971).
Sass, K.J. et al. Specificity in the correlation of verbal memory and hippocampal neuron loss: dissociation of memory, language and verbal intellectual ability. J. Clin. Exp. Neuropsychol. 14, 662–672 (1992).
Smith, D.H., Lowenstein, D.H., Gennarelli, T.A. & McIntosh, T.K. Persistent memory dysfunction is associated with bilateral hippocampal damage following experimental brain injury. Neurosci. Lett. 168, 151–154 (1994).
Lothman, E.W., Stringer, J.L. & Bertram, E.H. The dentate gyrus as a control point for seizures in the hippocampus and beyond. Epilepsy Res. Suppl. 7, 301–313 (1992).
Halasy, K. & Somogyi, P. Subdivisions in the multiple GABAergic innervation of granule cells in the dentate gyrus of the rat hippocampus. Eur. J. Neurosci. 5, 411–429 (1993).
Acknowledgements
We thank T. Pressler and R. Galán for helpful discussions; S. Jones and J. Frazier for helpful comments on the manuscript; and P. Puzerey for technical assistance. This work was supported by National Institutes of Health (NIH) Grant R01-NS33590 to B.W.S.
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The study was designed, data analyzed and manuscript written by P.L. and B.W.S. The experimental work was performed by P.L.
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Larimer, P., Strowbridge, B. Representing information in cell assemblies: persistent activity mediated by semilunar granule cells. Nat Neurosci 13, 213–222 (2010). https://doi.org/10.1038/nn.2458
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DOI: https://doi.org/10.1038/nn.2458
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