Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons

The perforant-path projection to the hippocampus forms synapses in the apical tuft of CA1 pyramidal neurons. We used computer modeling to examine the function of these distal synaptic inputs, which led to three predictions that we confirmed in experiments using rat hippocampal slices. First, activation of CA1 neurons by the perforant path is limited, a result of the long distance between these inputs and the soma. Second, activation of CA1 neurons by the perforant path depends on the generation of dendritic spikes. Third, the forward propagation of these spikes is unreliable, but can be facilitated by modest activation of Schaffer-collateral synapses in the upper apical dendrites. This 'gating' of dendritic spike propagation may be an important activation mode of CA1 pyramidal neurons, and its modulation by neurotransmitters or long-term, activity-dependent plasticity may be an important feature of dendritic integration during mnemonic processing in the hippocampus.

[1]  E. Kandel,et al.  ELECTROPHYSIOLOGY OF HIPPOCAMPAL NEURONS: IV. FAST PREPOTENTIALS. , 1961, Journal of neurophysiology.

[2]  W Rall,et al.  Changes of action potential shape and velocity for changing core conductor geometry. , 1974, Biophysical journal.

[3]  F. F. Weight,et al.  Perforant pathway activation of hippocampal CA1 stratum pyramidale neurons: Electrophysiological evidence for a direct pathway , 1982, Brain Research.

[4]  P. Schwartzkroin,et al.  Electrophysiology of Hippocampal Neurons , 1987 .

[5]  P Anderson,et al.  Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampus in vitro. , 1987, The Journal of physiology.

[6]  M. Yeckel,et al.  Feedforward excitation of the hippocampus by afferents from the entorhinal cortex: redefinition of the role of the trisynaptic pathway. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[7]  C. Koch,et al.  Effect of geometrical irregularities on propagation delay in axonal trees. , 1991, Biophysical journal.

[8]  Barry W. Connors,et al.  Functions of very distal dendrites: experimental and computational studies of layer 1 synapses on neocortical pyramidal cells , 1992 .

[9]  W B Levy,et al.  Electrophysiological and pharmacological characterization of perforant path synapses in CA1: mediation by glutamate receptors. , 1992, Journal of neurophysiology.

[10]  M. Stewart,et al.  Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea‐pig hippocampus. , 1992, The Journal of physiology.

[11]  D. Amaral.  Emerging principles of intrinsic hippocampal organization , 1993, Current Opinion in Neurobiology.

[12]  W. Levy,et al.  Ultrastructural identification of entorhinal cortical synapses in CA1 stratum lacunosum‐moleculare of the rat , 1994, Hippocampus.

[13]  R. Llinás,et al.  Intracellular study of direct entorhinal inputs to field CA1 in the isolated guinea pig brain in vitro , 1995, Hippocampus.

[14]  N. Spruston,et al.  Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. , 1995, Science.

[15]  G Buzsáki,et al.  Possible physiological role of the perforant path‐CA1 projection , 1995, Hippocampus.

[16]  U. Heinemann,et al.  The perforant path projection to hippocampal area CA1 in the rat hippocampal‐entorhinal cortex combined slice. , 1995, The Journal of physiology.

[17]  I. Soltesz.  Brief history of cortico‐hippocampal time with a special reference to the direct entorhinal input to CA1 , 1995, Hippocampus.

[18]  R. Empson,et al.  Perforant path connections to area CA1 are predominantly inhibitory in the rat hippocampal‐entorhinal cortex combined slice preparation , 1995, Hippocampus.

[19]  William B. Levy,et al.  Another network model bites the dust: Entorhinal inputs are no more than weakly excitatory in the hippocampal CA1 region , 1995, Hippocampus.

[20]  M. Yeckel,et al.  Monosynaptic excitation of hippocampal CA1 pyramidal cells by afferents from the entorhinal cortex , 1995, Hippocampus.

[21]  D. Johnston,et al.  Active properties of neuronal dendrites. , 1996, Annual review of neuroscience.

[22]  D. Johnston,et al.  Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons , 1996, The Journal of Neuroscience.

[23]  D. Johnston,et al.  K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons , 1997, Nature.

[24]  N. Spruston,et al.  Action potential initiation and backpropagation in neurons of the mammalian CNS , 1997, Trends in Neurosciences.

[25]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[26]  G. Buzsáki,et al.  Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus , 1998, The Journal of Neuroscience.

[27]  Nace L. Golding,et al.  Dendritic Sodium Spikes Are Variable Triggers of Axonal Action Potentials in Hippocampal CA1 Pyramidal Neurons , 1998, Neuron.

[28]  B. Sakmann,et al.  A new cellular mechanism for coupling inputs arriving at different cortical layers , 1999, Nature.

[29]  Daniel Johnston,et al.  Regulation of back-propagating action potentials in hippocampal neurons , 1999, Current Opinion in Neurobiology.

[30]  N. Spruston,et al.  Diversity and dynamics of dendritic signaling. , 2000, Science.

[31]  J. Magee,et al.  Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons , 2000, Nature Neuroscience.

[32]  M. Häusser,et al.  Dendritic coincidence detection of EPSPs and action potentials , 2001, Nature Neuroscience.

[33]  Nace L. Golding,et al.  Compartmental Models Simulating a Dichotomy of Action Potential Backpropagation in Ca1 Pyramidal Neuron Dendrites , 2001, Journal of neurophysiology.

[34]  T. Freund,et al.  Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells , 2001, Neuroscience.

[35]  Menno P. Witter,et al.  Place Cells and Place Recognition Maintained by Direct Entorhinal-Hippocampal Circuitry , 2002, Science.

[36]  Nace L. Golding,et al.  Dendritic spikes as a mechanism for cooperative long-term potentiation , 2002, Nature.

[37]  E. Schuman,et al.  Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons , 2002, Nature.

[38]  Bartlett W. Mel,et al.  Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell , 2003, Neuron.

[39]  T. Sejnowski,et al.  Synaptic background noise controls the input/output characteristics of single cells in an in vitro model of in vivo activity , 2003, Neuroscience.

[40]  Michele Migliore,et al.  Role of an A-Type K+ Conductance in the Back-Propagation of Action Potentials in the Dendrites of Hippocampal Pyramidal Neurons , 1999, Journal of Computational Neuroscience.

[41]  W. Senn,et al.  Top-down dendritic input increases the gain of layer 5 pyramidal neurons. , 2004, Cerebral cortex.

[42]  J. Magee,et al.  On the Initiation and Propagation of Dendritic Spikes in CA1 Pyramidal Neurons , 2004, The Journal of Neuroscience.

[43]  Daniel Johnston,et al.  LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites , 2004, Nature Neuroscience.

[44]  P. Andersen,et al.  Mode of activation of hippocampal pyramidal cells by excitatory synapses on dendrites , 2004, Experimental Brain Research.

[45]  B. McNaughton,et al.  Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge , 2004, Experimental Brain Research.

[46]  R. K. Simpson.  Nature Neuroscience , 2022 .