Principles Governing the Operation of Synaptic Inhibition in Dendrites

Cortical inhibitory interneurons (INs) are subdivided into a variety of morphologically and functionally specialized cell types. How the respective specific properties translate into mechanisms that regulate sensory-evoked responses of pyramidal neurons (PNs) remains unknown. Here, we investigated how INs located in cortical layer 1 (L1) of rat barrel cortex affect whisker-evoked responses of L2 PNs. To do so we combined in vivo electrophysiology and morphological reconstructions with computational modeling. We show that whisker-evoked membrane depolarization in L2 PNs arises from highly specialized spatiotemporal synaptic input patterns. Temporally L1 INs and L2-5 PNs provide near synchronous synaptic input. Spatially synaptic contacts from L1 INs target distal apical tuft dendrites, whereas PNs primarily innervate basal and proximal apical dendrites. Simulations of such constrained synaptic input patterns predicted that inactivation of L1 INs increases trial-to-trial variability of whisker-evoked responses in L2 PNs. The in silico predictions were confirmed in vivo by L1-specific pharmacological manipulations. We present a mechanism-consistent with the theory of distal dendritic shunting-that can regulate the robustness of sensory-evoked responses in PNs without affecting response amplitude or latency.echanistic understanding of the principles that underlie sensory-evoked neuronal responses remains a key challenge in neuroscience research. Although electrophysiological and optical imaging techniques provide access to activity patterns of individual and/or populations of neurons in live animals, information about the organization of the underlying synaptic input patterns that drive neuronal activity remains scarce. Here, we investigate the mechanisms underlying whisker deflection-evoked responses in pyramidal neurons (PNs) in the vibrissal part of rat primary somatosensory cortex (vS1, i.e., barrel cortex) (1). Specifically, we wanted to know whether and how L1 interneurons (INs) shape responses of L2 PNs. L1 is densely populated by apical tuft dendrites from multiple types of excitatory PNs and a sparse population of GABAergic INs (2). Recent studies in acute parasagittal (3) and coronal (4) brain slices in vitro have shown that L1 INs have axonal projections largely confined to L1, where they form synaptic connections with the dendrites from PNs located in L2/3 (5) and L5 (4). These connections place L1 INs in a perfect position to manipulate the activity of PNs, for example, by feed-forward inhibition and/or more indirect mechanisms such as disinhibition (4, 6). However, the influence of L1 INs on the sensory-evoked responses of PNs remains unclear.To address this, we performed whole-cell patch-clamp recordings in vivo and reconstructed the 3D morphologies of the recorded L1 INs. These data, acquired under the same experimental conditions as previously used to determine whisker-evoked spiking and 3D morphologies for PN cell types (7), were used to inform and constrain simulation experiments. Specifically, we...

Section: Significancesupporting

confidence: 74%

Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

Egger

Schmitt

Wallace

et al. 2015

“…For example, Koch et al proposed the proximal (on-path) inhibition could yield the strongest effects on the excitation (43). In contrast, Gidon and Segev predicted that distal inhibition could better "shunt" a group of excitatory synapses (56). Here, we tested similar ideas in our simulations (SI Appendix, Fig.…”

Section: Discussionmentioning

confidence: 78%

Cell-type–specific inhibition of the dendritic plateau potential in striatal spiny projection neurons

Lindroos

et al. 2017

Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dualcolor uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a celltype-specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg 2+ block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.O ne of the principal functions of neurons is to integrate excitatory and inhibitory synaptic inputs and transform subthreshold membrane potential fluctuations into suprathreshold spiking activities. Both theoretical and experimental works have proposed that a single neuron can process inputs as a multilayer computational device in which individual dendritic branches function as a computational unit and can generate dendritic spikes or plateau potentials (1-4). In vivo studies have demonstrated that dendritic plateau potentials evoked by coincident inputs can amplify excitatory signals and enhance the capacity of learning and information storage at a specific branch (5-7). However, a majority of the understanding of dendritic computation is based on studies focusing on pyramidal cells of hippocampal and cortical areas. It is relatively less known whether these conclusions apply to the striatal neurons (8).The striatum, the main input nucleus of the basal ganglia, receives convergent glutamatergic inputs from the cortex and thalamus (9-11). The integration of these functionally distinct inputs is critical for fine movement control and action selection (12, 13). The principal neurons in the striatum-spiny projection neurons (SPNs)-display hyperpolarized membrane potentials (∼−80 mV) at rest, often referred to as the "down-state" (14, 15). It is generally believed that coherent cortical inputs can effectively depolarize SPNs and promote membrane potential transitions from a hyperpolarized down-state to a depolarized "up-state" (∼−55 mV), at which point action potentials can be generated (14-16). To achieve this ∼20-to 30-mV state transition, it has been estimated that a large number (hundreds to thousands) of active inputs would be required (14-17). Interestingly, striatal SPNs are capable of producing long-lasting plateau potentials following activation of spatially clustered and temporally synchronized excit...

“…The parameters of the drift-diffusion model can be easily mapped to properties of neural circuits: weights for positive and negative information could correspond to the efficacy of synapses feeding positive and negative information to the integrator. Alternatively, the vetoing of female response could be implemented by proper placement of inhibitory inputs in a dendritic tree (26). The near-perfect integration of information (Table 1) could be implemented as a recurrent network or through synaptic plasticity (27,28).…”

Section: Discussionmentioning

confidence: 99%

Asymmetrical integration of sensory information during mating decisions in grasshoppers

Clemens

Krämer

Ronacher

2014

Decision-making processes, like all traits of an organism, are shaped by evolution; they thus carry a signature of the selection pressures associated with choice behaviors. The way sexual communication signals are integrated during courtship likely reflects the costs and benefits associated with mate choice. Here, we study the evaluation of male song by females during acoustic courtship in grasshoppers. Using playback experiments and computational modeling we find that information of different valence (attractive vs. nonattractive) is weighted asymmetrically: while information associated with nonattractive features has large weight, attractive features add little to the decision to mate. Accordingly, nonattractive features effectively veto female responses. Because attractive features have so little weight, the model suggests that female responses are frequently driven by integration noise. Asymmetrical weighting of negative and positive information may reflect the fitness costs associated with mating with a nonattractive over an attractive singer, which are also highly asymmetrical. In addition, nonattractive cues tend to be more salient and therefore more reliable. Hence, information provided by them should be weighted more heavily. Our findings suggest that characterizing the integration of sensory information during a natural behavior has the potential to provide valuable insights into the selective pressures shaping decision-making during evolution.O ne crucial decision in the lifetime of an animal is the decision with whom to mate. The males of many animals have evolved elaborate traits to attract females (1). These traits often involve the production of calling or courtship songs (2-4). Females base their decision to engage in courtship and to mate on the properties of these signals. Though many different factors drive and constrain the evolution of behavioral decisions in general (5, 6), the way information is integrated in the context of mate selection may reflect the fitness costs and benefits associated with mate choice. These costs depend on the mating system, e.g., the abundance of potential mating partners, the likelihood and costs of multiple matings, direct benefits of mating, and the costs of assessing a potential mate (7-10).Here, we investigate the implementation of a decision-making strategy by studying the integration of song features during courtship in grasshoppers. Acoustic courtship in the species Chorthippus biguttulus involves bidirectional communication. Males produce calling songs consisting of a sequence of simple stereotyped subunits-30-50 syllable-pause pairs. The female waits until the end of this song and indicates her readiness to further engage in a courtship ritual by producing a response song that allows the male to localize and approach the female (11) (Fig. 1A). This phase of courtship constitutes a first, important preselection step before females make their final assessment of an approaching mating partner. Not responding or responding to a male calling from a distance i...