A Role for Synaptic Inputs at Distal Dendrites: Instructive Signals for Hippocampal Long-Term Plasticity

Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
Neuron (Impact Factor: 15.05). 01/2008; 56(5):866-79. DOI: 10.1016/j.neuron.2007.10.020
Source: PubMed


Synaptic potentials originating at distal dendritic locations are severely attenuated when they reach the soma and, thus, are poor at driving somatic spikes. Nonetheless, distal inputs convey essential information, suggesting that such inputs may be important for compartmentalized dendritic signaling. Here we report a new plasticity rule in which stimulation of distal perforant path inputs to hippocampal CA1 pyramidal neurons induces long-term potentiation at the CA1 proximal Schaffer collateral synapses when the two inputs are paired at a precise interval. This subthreshold form of heterosynaptic plasticity occurs in the absence of somatic spiking but requires activation of both NMDA receptors and IP(3) receptor-dependent release of Ca(2+) from internal stores. Our results suggest that direct sensory information arriving at distal CA1 synapses through the perforant path provide compartmentalized, instructive signals that assess the saliency of mnemonic information propagated through the hippocampal circuit to proximal synapses.

Download full-text


Available from: Joshua T Dudman, Jan 30, 2014
  • Source
    • "Cooperative-Competitive Influence of EC and CA3 on CA1 Output The firing rate changes of CA3 and EC3 principal cells can at least partially account for the CA1 firing patterns and gamma oscillations we observed both across brain states and in the T maze task. These two major inputs can either cooperate or compete, depending on the nature of the task (Dvorak-Carbone and Schuman, 1999a, 1999b; Remondes and Schuman, 2002; Golding et al., 2002; Dudman et al., 2007; Han and Heinemann, 2013). During the recall phase (center arm) of the T maze task, the CA3 and EC3 inputs may cooperatively increase their influence on CA1 (Montgomery and Buzsá ki, 2007; Yamamoto et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Precisely how rhythms support neuronal communication remains obscure. We investigated interregional coordination of gamma oscillations using high-density electrophysiological recordings in the rat hippocampus and entorhinal cortex. We found that 30-80 Hz gamma dominated CA1 local field potentials (LFPs) on the descending phase of CA1 theta waves during navigation, with 60-120 Hz gamma at the theta peak. These signals corresponded to CA3 and entorhinal input, respectively. Above 50 Hz, interregional phase-synchronization of principal cell spikes occurred mostly for LFPs in the axonal target domain. CA1 pyramidal cells were phase-locked mainly to fast gamma (>100 Hz) LFP patterns restricted to CA1, which were strongest at the theta trough. While theta phase coordination of spiking across entorhinal-hippocampal regions depended on memory demands, LFP gamma patterns below 100 Hz in the hippocampus were consistently layer specific and largely reflected afferent activity. Gamma synchronization as a mechanism for interregional communication thus rapidly loses efficacy at higher frequencies.
    Full-text · Article · Sep 2014 · Neuron
  • Source
    • "Stimulation of perforant path inputs to hippocampal CA1 pyramidal neurons induces long-term potentiation at the Schaffer collaterals-CA1 synapses when the first precedes the second by 20 ms (Dudman et al., 2007). Therefore, we were interested in how lesion in one of the pathways may modify synaptic transmission in the other. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The hippocampal CA1 field processes spatial information, but the relative importance of intra- vs. extra-hippocampal sources of input into CA1 for spatial behavior is unclear. To characterize the relative roles of these two sources of input, originating in the hippocampal field CA3 and in the medial entorhinal cortex (MEC), we studied effects of discrete neurotoxic lesions of CA3 or MEC on concurrent spatial and nonspatial navigation tasks, and on synaptic transmission in afferents to CA1. Lesions in CA3 or MEC regions that abolished CA3-CA1, or reduced MEC-CA1 synaptic transmission, respectively, impaired spatial navigation and unexpectedly interfered with cue response, suggesting that in certain conditions of training regimen, hippocampal activity may influence behavior otherwise supported by nonhippocampal neural networks. MEC lesions had milder and temporary behavioral effects, but also markedly amplified transmission in the CA3-CA1 pathway. Extensive behavioral training had a similar, but more modest effect on CA3-CA1 transmission. Thus, cortical input to the hippocampus modulates CA1 activity both directly and indirectly, through heterosynaptic interaction, to control information flow in the hippocampal loop. Following damage to hippocampal cortical input, the functional coupling of separate intra- and extra-hippocampal inputs to CA1 involved in normal learning may initiate processes that support recovery of behavioral function. Such a process may explain how CA3 lesions, which do not significantly modify the basic features of CA1 neural activity, nonetheless impair spatial recall, whereas lesions of EC input to CA1, which reduce the spatial selectivity of CA1 firing in foraging rats, have only mild effects on spatial navigation.
    Full-text · Article · Aug 2014 · Frontiers in Behavioral Neuroscience
  • Source
    • "Action potential firing was extracellularly monitored (Chevaleyre and Castillo, 2003) or recorded in individual pyramidal cells (Younts et al., 2013), and was increased with both iLTD inducing protocols. The second effect, i.e., a direct increase in the amplitude of SC EPSP, was reported recently by two studies using a paired stimulation between proximal (SC) and distal perforant path (PP) excitatory inputs, termed input-timing dependent plasticity (ITDP; Dudman et al., 2007). The initial study showed that the pairing protocol induced a potentiation of SC-EPSPs, and that this potentiation is dependent on eCB-mediated LTD at inhibitory synapses (Xu et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Learning is believed to depend on lasting changes in synaptic efficacy such as long-term potentiation and long-term depression. As a result, a profusion of studies has tried to elucidate the mechanisms underlying these forms of plasticity. Traditionally, experience-dependent changes at excitatory synapses were assumed to underlie learning and memory formation. However, with the relatively more recent investigation of inhibitory transmission, it had become evident that inhibitory synapses are not only plastic, but also provide an additional way to modulate excitatory transmission and the induction of plasticity at excitatory synapses. Thanks to recent technological advances, progress has been made in understanding synaptic transmission and plasticity from particular interneuron subtypes. In this review article, we will describe various forms of synaptic plasticity that have been ascribed to two fairly well characterized populations of interneurons in the hippocampus, those expressing cholecystokinin (CCK) and parvalbumin (PV). We will discuss the resulting changes in the strength and plasticity of excitatory transmission that occur in the local circuit as a result of the modulation of inhibitory transmission. We will focus on the hippocampus because this region has a relatively well-understood circuitry, numerous forms of activity-dependent plasticity and a multitude of identified interneuron subclasses.
    Full-text · Article · Mar 2014 · Frontiers in Cellular Neuroscience
Show more