Distal Dendritic Inputs Control Neuronal Activity by Heterosynaptic Potentiation of Proximal Inputs

Abstract

Synaptic inputs onto distal dendritic tufts are believed to function by modulating time-locked proximal inputs. However, little is known about the function of these inputs when proximal synapses are not coincident or silent. Surprisingly we found that activation of apical tuft synapses alone resulted in heterosynaptic potentiation of proximal synapses. In mouse adult hippocampal CA1 pyramidal neurons, we show that activation of distal inputs from the entorhinal cortex specifically strengthens proximal synapses projecting from CA3. This AMPA receptor-mediated potentiation is accompanied by increased synaptic GluN2B-containing NMDA receptors, which are normally restricted to juvenile animals. These two synaptic modifications interact to generate striking bi-directional metaplastic changes. Heterosynaptically potentiated synapses become resistant to subsequent long-term potentiation (LTP) as the two forms of AMPA receptor-mediated potentiation mutually occlude. However this is only true when the LTP induction protocol is relatively weak. When it is strong and repeated, the magnitude of LTP after heterosynaptic plasticity is greatly increased, specifically through the activation of GluN2B-containing NMDA receptors. Thus in addition to strengthening proximal apical synapses, heterosynaptic plasticity shifts the input-selectivity of CA1 neurons and expands the dynamic range of LTP, resulting in neurons that are tuned to greatly potentiate strong CA3 inputs. These results show that one set of inputs can exert long-lasting heterosynaptic control over another, allowing the interplay of two functionally and spatially distinct pathways, thereby greatly expanding the repertoire of cellular and network plasticity.

Dendritic Organization of Olfactory Inputs to Medial Amygdala Neurons

“…Previous data suggest that, in contrast to synapses in the MOB, a large number of AOB synapses are rich in the GluN2B subunit of NMDARs (Dani et al, 2010). Whether similar rules apply to AOB and CoA synapses on MeA neurons awaits future studies using dendritic recording (Andrasfalvy and Magee, 2001) or nanoscale imaging of labeled glutamate receptors at these synapses (Nicholson et al, 2006;Dani et al, 2010). Moreover, potential spillover of glutamate to neighboring extrasynaptic NMDARs, which is thought to promote the generation of dendritic NMDA spikes (Chalifoux and Carter, 2011), may also play a part.…”

“…Previous studies in pyramidal neurons have shown that distal synapses can impact the gain and plasticity of proximal inputs (Remondes and Schuman, 2002;Dudman et al, 2007;Han and Heinemann, 2013). In CA1 pyramidal neurons, for instance, closely timed activation of the distal perforant path and the proximal Schaffer-collateral synapses induces potentiation of the latter (Dudman et al, 2007). Thus, it is likely that, through a similar mechanism, an association between main and accessory olfactory inputs will be formed in MeA principal neurons, leading to odor-evoked responses driven by pheromonal cues.…”

“…Moreover, other contributing mechanisms may include differences in the number, density, or subunit composition of NMDARs at these two synapses (Otmakhova et al, 2002;Nicholson et al, 2006). Previous data suggest that, in contrast to synapses in the MOB, a large number of AOB synapses are rich in the GluN2B subunit of NMDARs (Dani et al, 2010). Whether similar rules apply to AOB and CoA synapses on MeA neurons awaits future studies using dendritic recording (Andrasfalvy and Magee, 2001) or nanoscale imaging of labeled glutamate receptors at these synapses (Nicholson et al, 2006;Dani et al, 2010).…”

Theta Phase Segregation of Input-Specific Gamma Patterns in Entorhinal-Hippocampal Networks

“…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 Heineman, 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 Buzsáki, 2007; Yamamoto et al, 2014).…”

Bi-directional interplay between proximal and distal inputs to CA2 pyramidal neurons

“…Theta-burst stimulation of distal CA1 input induces a LTP of proximal input without affecting distal inputs, while low frequency stimulation of distal inputs induces LTD at distal inputs and LTP at proximal inputs (Han & Heinemann, 2013;Wöhrl, Haebler, & Heinemann, 2007). Furthermore, in area CA2 we have shown that HFS of proximal input induces iLTD allowing a lasting increase in both the E/I ratio and the firing of CA2 neurons in response to both proximal and distal excitatory input stimulation (Nasrallah et al, 2015;Piskorowski & Chevaleyre, 2013).…”