Dendritic integration of sensory and reward information facilitates learning

Learning goal-directed behaviours requires integration of separate information streams representing context, relevant stimuli and reward. Dendrites of pyramidal neurons are suitable sites for such integration, but it remains elusive how their responses adapt when an animal learns a new task. Here, we identify two distinct classes of dendritic responses that represent either contextual/sensory information or reward information and that differ in their task- and learning-related dynamics. Using longitudinal calcium imaging of apical dendritic tufts of L5 pyramidal neurons in mouse barrel cortex, we tracked dendritic activity across learning and analyzed both local dendritic branch signals and global apical tuft activity. During texture discrimination learning, sensory representations (including contextual and touch information) strengthened and converged on the reward-predicting tactile stimulus when mice became experts. In contrast, reward-associated responses were particularly strong in the naive condition and became less pronounced upon learning. When we blocked the representation of unexpected reward in naive animals with optogenetic inhibition, animals failed to learn until we released the block and learning proceeded normally. Our results suggest that reward signals in dendrites are essential for adjusting neuronal integration of converging inputs to facilitate adaptive behaviour.

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Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

Molecular Brain ◽

10.1186/s13041-021-00775-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Layer 4 ◽

Dendritic Complexity ◽

Cortex System

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2112212118 ◽

2021 ◽

Vol 118 (52) ◽

pp. e2112212118

Author(s):

Jiseok Lee ◽

Joanna Urban-Ciecko ◽

Eunsol Park ◽

Mo Zhu ◽

Stephanie E. Myal ◽

...

Keyword(s):

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Learning Task ◽

Early Gene ◽

Sensory Stimuli ◽

Association Learning ◽

Neural Ensembles ◽

Dependent Learning

Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on “engrams” in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience-dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity-dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP− neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.

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Loss of Calretinin in L5a Impairs the Formation of the Barrel Cortex Leading to Abnormal Behaviors

10.21203/rs.3.rs-233483/v1 ◽

2021 ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Abnormal Behaviors ◽

Dendritic Complexity ◽

Cortex System

Abstract The rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. L5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of L5a in the development of the barrel cortex remains unclear. Previously, we found that Calretinin is dynamically expressed in L5a. In this study, we analyzed Cr KO mice and found that the dendritic complexity and length of L5a pyramidal neurons were significantly decreased after Cr ablation. The membrane excitability and excitatory synaptic transmission of L5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, L4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Cr KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of L5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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Higher order thalamus encodes correct goal-directed action

10.1101/2020.07.05.188821 ◽

2020 ◽

Author(s):

D. LaTerra ◽

S. Petryszyn ◽

Marius Rosier ◽

L.M. Palmer

Keyword(s):

Sensory Processing ◽

Action Potentials ◽

Tactile Stimulus ◽

Pyramidal Neurons ◽

Sensory Information ◽

Axonal Projections ◽

Sustained Action ◽

Patch Clamp Electrophysiology ◽

Goal Directed Behavior

ABSTRACTThe thalamus is the gateway to the cortex. Cortical encoding of sensory information can therefore only be understood by considering the influence of thalamic processing on sensory input. Despite modulating sensory processing, little is known about the role of the thalamus during sensory-based behavior, let alone goal-directed behavior. Here, we use two-photon Ca2+ imaging, patch-clamp electrophysiology and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the primary somatosensory cortex (forepaw S1) during sensory processing and goal-directed behavior. We demonstrate that POm axons are active during tactile stimulus and increase activity specifically during the response and, to a lesser extent, reward epochs of a tactile goal-directed task. Furthermore, POm axons in forepaw S1 preferentially signaled correct behavior, with greatest activity during HIT responses. This activity is important for behavioral performance, as photoinhibition of archaerhodopsin-expressing neurons in the POm decreased overall behavioral success. Direct juxtacelluar recordings in the awake state illustrates POm neurons fire sustained action potentials during tactile stimulus. This tactile-evoked POm firing pattern was used during ChR2 photoactivation of POm axons in forepaw S1, revealing that action potentials in layer 2/3 (L2/3) pyramidal neurons are inhibited during sustained POm input. Taken together, POm axonal projections in forepaw S1 encode correct goal-directed active behavior, leading to GABAA-mediated inhibition of L2/3 pyramidal neurons.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1518773112 ◽

2015 ◽

Vol 112 (45) ◽

pp. 14072-14077 ◽

Cited By ~ 18

Author(s):

Robert Egger ◽

Arno C. Schmitt ◽

Damian J. Wallace ◽

Bert Sakmann ◽

Marcel Oberlaender ◽

...

Keyword(s):

Synaptic Input ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Cell Types ◽

Cortical Layer ◽

Evoked Responses ◽

Apical Tuft ◽

Sensory Evoked ◽

Pharmacological Manipulations

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.

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Sensory stimulus evoked responses in layer 2/3 pyramidal neurons of the hind paw-related mouse primary somatosensory cortex

10.1101/2020.08.30.274308 ◽

2020 ◽

Author(s):

Guillaume Bony ◽

Arjun A Bhaskaran ◽

Katy Le Corf ◽

Andreas Frick

Keyword(s):

Information Processing ◽

Somatosensory Cortex ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Primary Somatosensory Cortex ◽

List Type ◽

Evoked Responses ◽

Spontaneous Firing ◽

Layer 2

ABSTRACTThe mouse primary somatosensory cortex (S1) processes tactile sensory information and is the largest neocortex area emphasizing the importance of this sensory modality for rodent behavior. Most of our knowledge regarding information processing in S1 stems from studies of the whisker-related barrel cortex (S1–BC), yet the processing of tactile inputs from the hind-paws is poorly understood. We used in vivo whole-cell patch-clamp recordings from layer (L) 2/3 pyramidal neurons (PNs) of the S1 hind-paw (S1-HP) region of anaesthetized wild type (WT) mice to investigate their evoked sub- and supra-threshold activity, intrinsic properties, and spontaneous activity. Approximately 45% of these L2/3 PNs responded to brief contralateral HP stimulation in a subthreshold manner, ~5% fired action potentials, and ~50% of L2/3 PNs did not respond at all. The evoked subthreshold responses had long onset- (~23 ms) and peak-latencies (~61 ms). The majority (86%) of these L2/3 PNs responded to prolonged (stance-like) HP stimulation with both on- and off-responses. HP stimulation responsive L2/3 PNs had a greater intrinsic excitability compared to non-responsive ones, possibly reflecting differences in their physiological role. Similar to S1-BC, L2/3 PNs displayed up- and down-states, and low spontaneous firing rates (~0.1 Hz). Our findings support a sparse coding scheme of operation for S1–HP L2/3 PNs and highlight both differences and similarities with L2/3 PNs from other somatosensory cortex areas.KEY POINTSResponses of layer (L) 2/3 pyramidal neurons (PNs) of the primary somatosensory hind-paw cortex (S1-HP) to contralateral hind-paw stimulation reveal both differences and similarities compared to those of somatosensory neurons responding to other tactile (e.g. whiskers, forepaw, tongue) modalities.Similar to whisker-related barrel cortex (S1-BC) and forepaw cortex (S1-FP) S1-HP L2/3 PNs show a low spontaneous firing rate and a sparse action potential coding of evoked activity.In contrast to S1-BC, brief hind-paw stimulus evoked responses display a long latency in S1-HP neurons consistent with their different functional role.The great majority of L 2/3 PNs respond to prolonged hind-paw stimulation with both on- and off-responses.These results help us to better understand sensory information processing within layer 2/3 of the neocortex and the regional differences related to various tactile modalities.

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Olfactory modulation of barrel cortex activity during active whisking and passive whisker stimulation

10.21203/rs.3.rs-289925/v1 ◽

2021 ◽

Author(s):

Anthony Renard ◽

Evan Harrell ◽

Brice Bathallier

Keyword(s):

Facial Nerve ◽

Calcium Imaging ◽

Tactile Stimulation ◽

Barrel Cortex ◽

Neuronal Responses ◽

Population Activity ◽

Tactile Information ◽

Large Populations ◽

Whisker Stimulation ◽

The Impact

Abstract Rodents depend on olfaction and touch to meet many of their fundamental needs. The joint significance of these sensory systems is underscored by an intricate coupling between sniffing and whisking. However, the impact of simultaneous olfactory and tactile inputs on sensory representations in the cortex remains elusive. To study these interactions, we recorded large populations of barrel cortex neurons using 2-photon calcium imaging in head-fixed mice during olfactory and tactile stimulation. We find that odors alter barrel cortex activity in at least two ways, first by enhancing whisking, and second by central cross-talk that persists after whisking is abolished by facial nerve sectioning. Odors can either enhance or suppress barrel cortex neuronal responses, and while odor identity can be decoded from population activity, it does not interfere with the tactile representation. Thus, barrel cortex represents olfactory information which, in the absence of learned associations, is coded independently of tactile information.

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Detection of tactile inputs in the rat vibrissa pathway

Journal of Neurophysiology ◽

10.1152/jn.00004.2012 ◽

2012 ◽

Vol 108 (2) ◽

pp. 479-490 ◽

Cited By ~ 21

Author(s):

Douglas R. Ollerenshaw ◽

Bilal A. Bari ◽

Daniel C. Millard ◽

Lauren E. Orr ◽

Qi Wang ◽

...

Keyword(s):

High Speed ◽

Barrel Cortex ◽

Sensory Information ◽

Reaction Times ◽

Response Probability ◽

Relevant Information ◽

Relative Strength ◽

Spatiotemporal Representation ◽

Induced Motion ◽

Electrophysiological Findings

The rapid detection of sensory inputs is crucial for survival. Sensory detection explicitly requires the integration of incoming sensory information and the ability to distinguish between relevant information and ongoing neural activity. In this study, head-fixed rats were trained to detect the presence of a brief deflection of their whiskers resulting from a focused puff of air. The animals showed a monotonic increase in response probability and a decrease in reaction time with increased stimulus strength. High-speed video analysis of whisker motion revealed that animals were more likely to detect the stimulus during periods of reduced self-induced motion of the whiskers, thereby allowing the stimulus-induced whisker motion to exceed the ongoing noise. In parallel, we used voltage-sensitive dye (VSD) imaging of barrel cortex in anesthetized rats receiving the same stimulus set as those in the behavioral portion of this study to assess candidate codes that make use of the full spatiotemporal representation and to compare variability in the trial-by-trial nature of the cortical response and the corresponding variability in the behavioral response. By application of an accumulating evidence framework to the population cortical activity measured in separate animals, a strong correspondence was made between the behavioral output and the neural signaling, in terms of both the response probabilities and the reaction times. Taken together, the results here provide evidence for detection performance that is strongly reliant on the relative strength of signal versus noise, with strong correspondence between behavior and parallel electrophysiological findings.

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Widespread inhibition, antagonism, and synergy in mouse olfactory sensory neurons in vivo

10.1101/803908 ◽

2019 ◽

Cited By ~ 1

Author(s):

Shigenori Inagaki ◽

Ryo Iwata ◽

Masakazu Iwamoto ◽

Takeshi Imai

Keyword(s):

Sensory Neurons ◽

Calcium Imaging ◽

Odorant Receptor ◽

Sensory Information ◽

Olfactory Sensory Neurons ◽

Axon Terminals ◽

Two Photon ◽

Odor Mixtures ◽

The Brain

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.

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Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

Frontiers in Neuroanatomy ◽

10.3389/fnana.2020.605029 ◽

2020 ◽

Vol 14 ◽

Author(s):

Shin-Hwa Tsai ◽

Chih-Yu Tsao ◽

Li-Jen Lee

Keyword(s):

White Matter ◽

Mouse Model ◽

Pyramidal Neurons ◽

Sensory Information ◽

Morphological Characters ◽

Cortical Layer ◽

Type I ◽

Brain Functions ◽

Neuron Density ◽

Subplate Neurons

Increased white matter neuron density has been associated with neuropsychiatric disorders including schizophrenia. However, the pathogenic features of these neurons are still largely unknown. Subplate neurons, the earliest generated neurons in the developing cortex have also been associated with schizophrenia and autism. The link between these neurons and mental disorders is also not well established. Since cortical layer VIb neurons are believed to be the remnant of subplate neurons in the adult rodent brain, in this study, we aimed to examine the cytoarchitecture of neurons in cortical layer VIb and the underlying white matter in heterozygous Disc1 mutant (Het) mice, a mouse model of schizophrenia. In the white matter, the number of NeuN-positive neurons was quite low in the external capsule; however, the density of these cells was found increased (54%) in Het mice compared with wildtype (WT) littermates. The density of PV-positive neurons was unchanged in the mutants. In the cortical layer VIb, the density of CTGF-positive neurons increased (21.5%) in Het mice, whereas the number of Cplx3-positive cells reduced (16.1%) in these mutants, compared with WT mice. Layer VIb neurons can be classified by their morphological characters. The morphology of Type I pyramidal neurons was comparable between genotypes while the dendritic length and complexity of Type II multipolar neurons were significantly reduced in Het mice. White matter neurons and layer VIb neurons receive synaptic inputs and modulate the process of sensory information and sleep/arousal pattern. Aberrances of these neurons in Disc1 mutants implies altered brain functions in these mice.

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