Abnormal wiring of CCK+ basket cells disrupts spatial information coding

Pino, Isabel del; Brotons-Mas, Jorge R.; Marques-Smith, André; Marighetto, Aline; Frick, Andreas; Marı́n, Oscar; Rico, Beatriz

doi:10.1038/nn.4544

Cited by 79 publications

(69 citation statements)

References 63 publications

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“…Currently, only few attempts have been made to directly prove the role of timed interactions during development for the later emergence of network function and adult behavior. Recently, the key role of vasoactive intestinal peptide (VIP) and cholecystokinine (CCK)-positive interneurons for cortical circuit development has been demonstrated 56,57 . In the same line, our findings identify pyramidal neurons in layer II/III as generators of early activity, facilitating the coupling within local neocortical circuits and glutamatergic communication between upper and deeper layers 58 .…”

Section: Discussionmentioning

confidence: 99%

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Chini¹,

Lindemann²,

Ja³

et al. 2018

Preprint

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SUMMARYCognitive deficits, core features of mental illness, largely result from dysfunction of prefrontal-hippocampal networks. This dysfunction emerges already during early development, before a detectable behavioral readout, yet the cellular elements controlling the abnormal maturation are still unknown. Combining in vivo electrophysiology and optogenetics with neuroanatomy and pharmacology in neonatal mice mimicking the dual genetic - environmental etiology of psychiatric disorders, we identified pyramidal neurons in layer II/III of the prefrontal cortex as key elements causing disorganized oscillatory entrainment of local circuits in beta-gamma frequencies. Their abnormal firing rate and timing result from sparser dendritic arborization and lower spine density. Pharmacological modulation of aberrantly hyper-mature microglia rescues morphological, synaptic and functional neuronal deficits and restores the early circuit function. Elucidation of the cellular substrate of developmental miswiring related to later cognitive deficits opens new perspectives for identification of neurobiological targets, amenable to therapies.HighlightsMice mimicking the etiology of mental illness have dysregulated prefrontal networkStructural and synaptic deficits cause abnormal rate and timing of pyramidal firingWeaker activation of prefrontal circuits results from deficits of pyramidal neuronsRescue of microglial function restores developing prefrontal circuits

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Section: Discussionmentioning

confidence: 99%

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Chini¹,

Lindemann²,

Ja³

et al. 2018

Preprint

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“…Inhibitory interneurons play an integral role within the hippocampus controlling place cell activity (Del Pino et al, 2017; Royer et al, 2012; Sheffield et al, 2017; Trouche et al, 2016), where short-term changes in SST and PV interneuron activity differentially regulate the emergence and firing patterns of place cells (Royer et al, 2012; Sheffield et al, 2017) by controlling glutamatergic synaptic plasticity (Chiu et al, 2013; Schulz et al, 2018). But the consequences of long-term plasticity at inhibitory synapses on place cell activity has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

Udakis

Pedrosa

Clopath

et al. 2019

Preprint

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22The formation and maintenance of spatial representations within hippocampal cell assemblies 23 is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it 24 is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at 25 distinct inhibitory synapses and its regulation of hippocampal network activity is not well 26 understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin 27 expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD 28 and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type 29 calcium channel activation to confer synapse specificity but otherwise employ distinct 30 mechanisms. Since parvalbumin and somatostatin interneurons preferentially target 31 perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and 32 SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. 33 Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to 34 stabilise place cells while facilitating representation of multiple unique environments within 35 the hippocampal network.36 37 38 39 Keywords 40 Hippocampus, inhibition, plasticity, parvalbumin, somatostatin, LTD, LTP, STDP T-type 41 calcium channel. 42 102 term inhibitory plasticity have profound effects on the output of CA1 pyramidal neurons and 103use computational modelling to demonstrate that these plasticity rules can provide a 104 mechanism by which hippocampal place fields can remain stable over time whilst flexibly 105 encoding location in multiple environments. 106 Results 107Divergent inhibitory plasticity at PV and SST synapses 108 To achieve subtype specific control of inhibitory interneurons, we selectively activated either 109 PV or SST interneurons by expressing the light-activated cation channel channelrhodopsin-2 110 (ChR2) in a cre-dependent manner using mice that expressed cre recombinase under control of 111 the promoter for either the parvalbumin gene (PV-cre) or somatostatin gene (SST-cre) crossed 112 with mice expressing cre-dependent ChR2 (PV-ChR2 and SST-ChR2 mice; methods). 113Immunohistochemisty confirmed that ChR2 expression was highest in the Stratum Pyramidal 114 (SP) and Stratum Oriens (SO) layers for PV-ChR2 mice with cell bodies principally located in 115 SP (Figure 1A). Conversely, ChR2 expression was highest in the SO and Stratum Lacunosum 116 Moleculare (SLM) layers for SST-ChR2 mice with cell bodies principally located in SO 117 (Figure 1B). These expression profiles are consistent with the established roles of PV and SST 118 interneurons providing perisomatic and dendritic inhibition respectively (Booker and Vida, 119 2018; Klausberger and Somogyi, 2008; Pelkey et al., 2017). To further confirm the spatially 120 distinct inhibitory targets, we recorded interneuron subtype-specific inhibitory currents onto 121 CA1 pyramidal neurons by activating ChR2 with 470nm blue light (Figu...

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“…In light of the findings demonstrating the beneficial role of PE in mouse models of neurodevelopmental disorders such as Down syndrome and Rett syndrome (Begenisic, Sansevero, Baroncelli, Cioni, & Sale, 2015;Lonetti et al, 2010), a better understanding of the cellular and molecular changes promoted by early experiences is desirable. Moreover, considering that disruption of CCK+ cells connectivity impact the generation of theta oscillations and memory formation in adult (del Pino et al, 2017), establishing the mechanisms underlying the synaptic integration of this cell-type is also needed. In the present study, we demonstrate that among the varied inhibitory synapses in the DG, somatic CCK+ innervation is adjusted in response to cortical activity.…”

Section: Discussionmentioning

confidence: 99%

Experience-dependent inhibitory plasticity is mediated by CCK+ basket cells in the developing dentate gyrus

Feng

Alicea

Pham

et al. 2020

Preprint

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Early postnatal experience shapes both inhibitory and excitatory networks in the hippocampus. However, the underlying circuit plasticity is unclear. Using an enriched environment (EE) paradigm, we assessed the circuit plasticity of inhibitory cell-types in the hippocampus. We found that cholecystokinin (CCK)-expressing basket cells strongly increased somatic inhibition on the excitatory granular cells (GC) following EE while another pivotal inhibitory cell-type, parvalbumin (PV)-expressing cells did not show changes. By inhibiting activity of the entorhinal cortex (EC) using a chemogenetic approach, we demonstrate that the projections from the EC is responsible for the developmental plasticity of CCK+ basket cells. Our measurement of the input decorrelation by DG circuit suggests that EE has little effect on pattern separation despite of the altered CCK+ basket cell circuit. Altogether, our study places the activity-dependent remodeling of CCK+ basket cell innervation as a central process to adjust inhibition in the DG, while maintaining the computation in the circuit. Figure 5. PE housing has limited effect on pattern separation in the DG. (A) Top, cartoon depicting whole-cell recording of the GCs during simultaneous stimulation of the PP. Bottom, representative traces obtained in currentclamp mode in response to the stimulation with 5 input spike trains.To assess the level of pattern separation operated by single recorded GCs, the similarity of the inputs is compared to the similarity of the outputs using different comparative metrics. (B) Representative graphs of pattern separation with pairwise output similarity versus the pairwise input similarity measured by the three different metrics, including R, NDP and SF and using 10 ms bins. Data points below and above the dashed line correspond to pattern separation and pattern convergence, respectively. Solid lines represent the linear fits for the ANCOVA. Statistical comparisons were performed with an ANCOVA (the aoctool function in Matlab) and a two-sample t-test (*: p<0.05 and ***: p<0.001). (C) A summary for FR and p(Burst) (number of animals = 4 for both group, total 15 recordings for each group). Statistical comparisons were performed with a two-samples t-test for firing rate (t = 1.559, p = 0.13) and p(Burst) (t = 1.3627, p = 0.184). (D) Compactness, Occupancy or FR codes were measured for each recording sets. Statistical comparisons were performed with 2 sample t-test for binwise Compactness of output (t = 1.04, p = 0.307), the variations of Occupancy (t = 1.924, p = 0.073) and the variations in FR or spike trains (t = 1.129, p = 0.269). For each bars, the number of animals and the number of recorded cells used for the quantification are reported (a/n).

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Abnormal wiring of CCK+ basket cells disrupts spatial information coding

Cited by 79 publications

References 63 publications

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Microglia inhibition rescues developmental hypofrontality in a mouse model of mental illness

Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output

Experience-dependent inhibitory plasticity is mediated by CCK+ basket cells in the developing dentate gyrus

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