Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning

Túri, Gergely F.; Li, Wenke; Chavlis, Spyridon; Pandi, Ioanna; O’Hare, Justin K.; Priestley, James B.; Grosmark, Andres; Liao, Zhenrui; Ladow, Max; Zhang, Jeff F.; Zemelman, Boris V.; Poirazi, Panayiota; Losonczy, Attila

doi:10.1016/j.neuron.2019.01.009

Cited by 174 publications

(216 citation statements)

References 78 publications

(134 reference statements)

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“…S6D). This absence of synaptic depression is 10 inconsistent with the prediction of the standard voltage-dependent model ( Fig. 3D), but 11 instead favors the alternative model, which predicted that only previously potentiated 12 inputs would be eligible for synaptic depression, independent of postsynaptic voltage.…”

Section: D)mentioning

confidence: 59%

“…1, F to H). 9 When both initial ramp amplitude and relative input timing are considered, it is apparent 10 that the preferred conditions for large synaptic depression are that spatial inputs 1) have 11 already been strengthened by previous plasticity, resulting in elevated postsynaptic 12 depolarization at the time of presynaptic spikes, and 2) are activated within a time window 13 ~2 -4 seconds away from a plateau ( Fig. 1J, trace color indicates initial ramp amplitude; 14 Fig 1K; two-dimensional interpolation from data, trace color indicates change in ramp 15 amplitude, see Materials and Methods).…”

Section: D)mentioning

confidence: 99%

“…However, it was not clear 7 from previous experiments if short timescale correlations would modulate changes in 8 synaptic strength induced by BTSP, which may reveal similarities with other correlative 9 forms of plasticity. 10 In the current study, we sought to directly determine the dependence of BTSP on 11 the correlation of presynaptic activity and postsynaptic depolarization in individual place 12 cells. Intracellular voltage recordings from CA1 place cells were established in head-fixed 13 mice trained to run for a water reward on a circular treadmill decorated with visual and 14 tactile cues to distinguish spatial positions (187 cm in length).…”

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Bidirectional synaptic plasticity rapidly modifies hippocampal representations

Milstein

Bittner

et al. 2020

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15According to standard models of synaptic plasticity, correlated activity between 16 connected neurons drives changes in synaptic strengths to store associative 17 memories. Here we tested this hypothesis in vivo by manipulating the activity of 18 hippocampal place cells and measuring the resulting changes in spatial selectivity. 19 We found that the spatial tuning of place cells was rapidly reshaped via 20 bidirectional synaptic plasticity. To account for the magnitude and direction of 21 plasticity, we evaluated two models -a standard model that depended on 22 synchronous pre-and post-synaptic activity, and an alternative model that 23 1 depended instead on whether active synaptic inputs had previously been 1 potentiated. While both models accounted equally well for the data, they predicted 2 opposite outcomes of a perturbation experiment, which ruled out the standard 3 correlation-dependent model. Finally, network modeling suggested that this form 4 of bidirectional synaptic plasticity enables population activity, rather than pairwise 5 neuronal correlations, to drive plasticity in response to changes in the 6 environment. 7 8 Main Text 9 Activity-dependent changes in synaptic strength can flexibly alter the selectivity of 10 neuronal firing for particular features of the environment, providing a cellular substrate for 11 learning and memory. Various forms of Hebbian synaptic plasticity have been considered 12 for decades to be the main or even only synaptic plasticity mechanisms present within 13 most brain regions of a number of species. The core feature of such plasticity 14mechanisms is that they are autonomously driven by the repeated presence of correlated 15 presynaptic and postsynaptic activity that leads to either increases or decreases in 16 synaptic strength depending on the exact temporal coincidence (1-4). 17 The hippocampus plays an important role in many forms of learning and memory, 18 and the spatial firing rates of hippocampal place cells have been shown to change with 19 alterations in environmental context or the locations of salient features, like reward (5-20 11). Furthermore in CA1 neurons, place cell activity can emerge in a single trial following 21 a dendritic calcium spike (also called a plateau potential) (12-14). The form of synaptic 22 plasticity responsible for this rapid change in selectivity, termed behavioral timescale 23 2 synaptic plasticity (BTSP), modifies synaptic inputs active within a multi-second time 1 window around the plateau potential. That BTSP strengthens many synaptic inputs whose 2 activation did not cause or even coincide with postsynaptic activity suggests that it might 3 be a fundamentally different form of plasticity than classical correlation-driven Hebbian 4 plasticity (1-3). Such a plasticity rule could enable representation learning in cortical brain 5 regions like the hippocampus to be guided by delayed behavioral outcomes, rather than 6 by short timescale associations of neuronal input and output. However, it was not clear 7 from previous experiments...

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Section: D)mentioning

confidence: 59%

Section: D)mentioning

confidence: 99%

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Bidirectional synaptic plasticity rapidly modifies hippocampal representations

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Bittner

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“…Moreover, tuned by specific learning paradigms in relation to animal mood state and experience, such as reward [75] or goal-oriented behavior [76,77], VIP+ IS cells may play a role of an important modulator of microcircuit activity for information selection and encoding. Table 1).…”

Section: Discussionmentioning

confidence: 99%

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Luo

Guet-McCreight

Villette

et al. 2018

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In the hippocampus, a highly specialized population of vasoactive intestinal peptide (VIP)-expressing interneuron-specific (IS) inhibitory cells provides local circuit disinhibition via preferential innervation of different types of GABAergic interneurons.While disinhibition can be critical in modulating network activity and different forms of hippocampal learning, the synaptic and integrative properties of IS cells and their recruitment during network oscillations remain unknown. Using a combination of patchclamp recordings, photostimulation, computational modelling as well as recordings of network oscillations simultaneously with two-photon Ca 2+ -imaging in awake mice in vivo, we identified synaptic mechanisms that can control the firing of IS cells, and explored their impact on the cell recruitment during theta oscillations and sharp-waveassociated ripples. We found that IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, integrating their intrinsic and synaptic properties into computational models predicted recruitment of these cells during the rising to peak phases of theta oscillations and during ripples depending on inhibitory contributions. In vivo Ca 2+ -imaging in awake mice confirmed in part the theoretical predictions, revealing a significant speed modulation of IS cells and their preferential albeit delayed recruitment during theta-run epochs, with firing at the rising phase to peak of the theta cycle. However, it also uncovered that IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.3

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“…We used the same imaging system as described previously 28,48 . All images were acquired with a Nikon 40× NIR water-immersion objective (0.8 NA, 3.5 mm WD) in distilled water.…”

Section: In Vivo Two-photon Calcium Imagingmentioning

confidence: 99%

Synaptogenic activity of the axon guidance molecule Robo2 is critical for hippocampal circuit function

Blockus

Rolotti

Szoboszlay

et al. 2019

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The developmental transition between axon guidance and synapse formation is critical for circuit assembly but still poorly understood at the molecular level. We hypothesized that this key transition could be regulated by axon guidance cues switching their function to regulate synaptogenesis with subcellular specificity. Here, we report evidence for such a functional switch, describing a novel role for the axon guidance molecule Robo2 in excitatory synapse formation onto dendrites of CA1 pyramidal neurons (PNs) in the mouse hippocampus. Cell-autonomous deletion of Robo2 from CA1 PNs leads to a drastic reduction of the number of excitatory synapses specifically in proximal dendritic compartments. At the molecular level, we show that this novel postsynaptic function of Robo2 depends on both its canonical ligand Slit and a novel interaction with presynaptic Neurexins. Biophysical analysis reveals that Robo2 binds directly to Neurexins via itsIg4-5 domains. In vivo 2-photon Ca 2+ imaging of CA1 PNs during spatial navigation in mice shows that sparse deletion of Robo2 during development drastically reduces the likelihood of place cell emergence and alters spatial coding properties of the remaining place cells. Our results identify Robo2 as a novel molecular effector linking synaptic specificity to the acquisition of spatial coding properties characterizing hippocampal circuits.Proper circuit function relies on the establishment of synaptic connections characterized by a high degree of cell type and subcellular specificity. How this striking degree of synaptic specificity is achieved during development remains poorly understood, especially in the complex brains of mammals. Many cell surface molecules that mediate molecular recognition between axons and dendrites during circuit development have been identified 1-4 . These trans-synaptic adhesion molecules are often expressed in a cell-type specific manner 5 thereby determining the pool of a cell's possible synaptic partners. Some classes of these molecules have synaptic organizing properties evidenced by their direct or indirect ability to recruit key pre-and postsynaptic proteins. When axons reach their target areas, a cellular switch from a phase of growth and branching to synaptogenesis is observed. This switch is characterized by dynamic instability of adhesion progressively leading to more stable patterns of synaptic connectivity characterizing adult circuits. One of the foremost outstanding questions in neuroscience is how synapse formation is mechanistically integrated with earlier developmental steps such as axon guidance 3 and branching. One potential mechanism for coordinating this transition relies on the possibility that axon guidance cues acquire synaptogenic functions during circuit wiring. Indeed, evidence for such dual use of developmental molecules has been reported 6 . However, it remains unclear what prompts molecules to switch their function from axon guidance to synaptogenesis.Here we report that the well-studied axon guidance ligand-receptor pair Sl...

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Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning

Cited by 174 publications

References 78 publications

Bidirectional synaptic plasticity rapidly modifies hippocampal representations

Bidirectional synaptic plasticity rapidly modifies hippocampal representations

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Synaptogenic activity of the axon guidance molecule Robo2 is critical for hippocampal circuit function

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