Cholinergic modulation of sensory processing in awake mouse cortex

AbstractCholinergic modulation of brain activity is fundamental for awareness and conscious sensorimotor behaviours, but deciphering the timing and significance of acetylcholine actions for these behaviours is challenging. The widespread nature of cholinergic projections to the cortex means that new insights require access to specific neuronal populations, and on a time-scale that matches behaviourally relevant cholinergic actions. Here, we use fast, voltage imaging of L2/3 cortical pyramidal neurons exclusively expressing the genetically-encoded voltage indicator Butterfly 1.2, in awake, head-fixed mice, receiving sensory stimulation, whilst manipulating the cholinergic system. Altering muscarinic acetylcholine function re-shaped sensory-evoked fast depolarisation and subsequent slow hyperpolarisation of L2/3 pyramidal neurons. A consequence of this re-shaping was disrupted adaptation of the sensory-evoked responses, suggesting a critical role for acetylcholine during sensory discrimination behaviour. Our findings provide new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

Download Full-text

Tonic GABAergic activity facilitates dendritic calcium signaling and short-term plasticity

10.1101/2020.04.22.055137 ◽

2020 ◽

Author(s):

Chiayu Q. Chiu ◽

Thomas M. Morse ◽

Francesca Nani ◽

Frederic Knoflach ◽

Maria-Clemencia Hernandez ◽

...

Keyword(s):

Calcium Signaling ◽

Neuronal Excitability ◽

Pyramidal Neurons ◽

Calcium Influx ◽

Brain Activity ◽

Receptor Subtypes ◽

Short Term ◽

Dendritic Membrane ◽

Cortical Pyramidal Neurons ◽

Gabaergic Activity

SummaryBrain activity is highly regulated by GABAergic activity, which acts via GABAARs to suppress somatic spike generation as well as dendritic synaptic integration and calcium signaling. Tonic GABAergic conductances mediated by distinct receptor subtypes can also inhibit neuronal excitability and spike output, though the consequences for dendritic calcium signaling are unclear. Here, we use 2-photon calcium imaging in cortical pyramidal neurons and computational modeling to show that low affinity GABAARs containing an α5 subunit mediate a tonic hyperpolarization of the dendritic membrane potential, resulting in deinactivation of voltage-gated calcium channels and a paradoxical boosting of action potential-evoked calcium influx. We also find that GABAergic enhancement of calcium signaling modulates short-term synaptic plasticity, augmenting depolarization-induced suppression of inhibition. These results demonstrate a novel role for GABA in the control of dendritic activity and suggest a mechanism for differential modulation of electrical and biochemical signaling.

Download Full-text

Robust Encoding of Abstract Rules by Distinct Neuronal Populations in Primate Visual Cortex

10.1101/2020.10.28.351460 ◽

2020 ◽

Author(s):

Donatas Jonikaitis ◽

Nir Nissim ◽

Ruobing Xia ◽

Tirin Moore

Keyword(s):

Visual Cortex ◽

Sensory Information ◽

Sensory Stimulation ◽

Cognitive Factors ◽

Stimulus Selection ◽

Neuronal Populations ◽

Primate Visual Cortex ◽

Behavioral Constraints ◽

Sensory Responses ◽

Selection Of

AbstractIt is widely known that neural activity in sensory representations is modulated by cognitive factors such as attention, reward value and working memory. In such cases, sensory responses are found to reflect a selection of the specific sensory information needed to achieve behavioral goals. In contrast, more abstract behavioral constraints that do not involve stimulus selection, such as task rules, are thought to be encoded by neurons at later stages. We show that information about abstract rules is encoded by neurons in primate visual cortex in the absence of sensory stimulation. Furthermore, we show that rule information is greatest among neurons with the least visual activity and the weakest coupling to local neuronal networks. Our results identify rule-specific signals within a sensory representation and suggest that distinct mechanisms exist there for mapping rule information onto sensory guided decisions.

Download Full-text

Spatiotemporal structure of sensory-evoked and spontaneous activity revealed by mesoscale imaging in anesthetized and awake mice

10.1101/2020.05.22.111021 ◽

2020 ◽

Cited By ~ 1

Author(s):

Navvab Afrashteh ◽

Samsoon Inayat ◽

Edgar Bermudez Contreras ◽

Artur Luczak ◽

Bruce L. McNaughton ◽

...

Keyword(s):

Spontaneous Activity ◽

Brain Activity ◽

Activity Patterns ◽

Sensory Stimulation ◽

Wide Field ◽

Evoked Responses ◽

Evoked Activity ◽

Cortical Regions ◽

The One ◽

Sensory Evoked

AbstractBrain activity propagates across the cortex in diverse spatiotemporal patterns, both as a response to sensory stimulation and during spontaneous activity. Despite been extensively studied, the relationship between the characteristics of such patterns during spontaneous and evoked activity is not completely understood. To investigate this relationship, we compared visual, auditory, and tactile evoked activity patterns elicited with different stimulus strengths and spontaneous activity motifs in lightly anesthetized and awake mice using mesoscale wide-field voltage-sensitive dye and glutamate imaging respectively. The characteristics of cortical activity that we compared include amplitude, speed, direction, and complexity of propagation trajectories in spontaneous and evoked activity patterns. We found that the complexity of the propagation trajectories of spontaneous activity, quantified as their fractal dimension, is higher than the one from sensory evoked responses. Moreover, the speed and direction of propagation, are modulated by the amplitude during both, spontaneous and evoked activity. Finally, we found that spontaneous activity had similar amplitude and speed when compared to evoked activity elicited with low stimulus strengths. However, this similarity gradually decreased when the strength of stimuli eliciting evoked responses increased. Altogether, these findings are consistent with the fact that even primary sensory areas receive widespread inputs from other cortical regions, and that, during rest, the cortex tends to reactivate traces of complex, multi-sensory experiences that may have occurred in a range of different behavioural contexts.

Download Full-text

Atypical visual-auditory predictive coding in autism spectrum disorder: Electrophysiological evidence from stimulus omissions

Autism ◽

10.1177/1362361320926061 ◽

2020 ◽

Vol 24 (7) ◽

pp. 1849-1859

Author(s):

Thijs van Laarhoven ◽

Jeroen J Stekelenburg ◽

Mart LJM Eussen ◽

Jean Vroomen

Keyword(s):

Autism Spectrum Disorder ◽

Brain Activity ◽

Predictive Coding ◽

Sensory Information ◽

Sensory Stimulation ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Prediction Errors ◽

Typical Development ◽

Autism Spectrum Disorder Group

Autism spectrum disorder is a pervasive neurodevelopmental disorder that has been linked to a range of perceptual processing alterations, including hypo- and hyperresponsiveness to sensory stimulation. A recently proposed theory that attempts to account for these symptoms, states that autistic individuals have a decreased ability to anticipate upcoming sensory stimulation due to overly precise internal prediction models. Here, we tested this hypothesis by comparing the electrophysiological markers of prediction errors in auditory prediction by vision between a group of autistic individuals and a group of age-matched individuals with typical development. Between-group differences in prediction error signaling were assessed by comparing event-related potentials evoked by unexpected auditory omissions in a sequence of audiovisual recordings of a handclap in which the visual motion reliably predicted the onset and content of the sound. Unexpected auditory omissions induced an increased early negative omission response in the autism spectrum disorder group, indicating that violations of the prediction model produced larger prediction errors in the autism spectrum disorder group compared to the typical development group. The current results show that autistic individuals have alterations in visual-auditory predictive coding, and support the notion of impaired predictive coding as a core deficit underlying atypical sensory perception in autism spectrum disorder. Lay abstract Many autistic individuals experience difficulties in processing sensory information (e.g. increased sensitivity to sound). Here we show that these difficulties may be related to an inability to process unexpected sensory stimulation. In this study, 29 older adolescents and young adults with autism and 29 age-matched individuals with typical development participated in an electroencephalography study. The electroencephalography study measured the participants’ brain activity during unexpected silences in a sequence of videos of a handclap. The results showed that the brain activity of autistic individuals during these silences was increased compared to individuals with typical development. This increased activity indicates that autistic individuals may have difficulties in processing unexpected incoming sensory information, and might explain why autistic individuals are often overwhelmed by sensory stimulation. Our findings contribute to a better understanding of the neural mechanisms underlying the different sensory perception experienced by autistic individuals.

Download Full-text

Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type

10.1101/216085 ◽

2017 ◽

Cited By ~ 2

Author(s):

Eszter Boldog ◽

Trygve Bakken ◽

Rebecca D. Hodge ◽

Mark Novotny ◽

Brian D. Aevermann ◽

...

Keyword(s):

Pyramidal Neurons ◽

Cortical Layer ◽

Molecular Signature ◽

Gabaergic Interneuron ◽

Cell Type ◽

Human Cortex ◽

Dendritic Computation ◽

Mouse Cortex ◽

Cortical Pyramidal Neurons ◽

Single Nucleus

AbstractWe describe convergent evidence from transcriptomics, morphology and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a novel group of human interneurons with anatomical features never described in rodents having large, “rosehip”-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1/CCK-positive, CNR1/SST/CALB2/PVALB-negative) matching a single transcriptomically-defined cell type whose molecular signature is not seen in mouse cortex. Rosehip cells make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.

Download Full-text

Ipsilateral finger representations in the sensorimotor cortex are driven by active movement processes, not passive sensory input

Journal of Neurophysiology ◽

10.1152/jn.00439.2018 ◽

2019 ◽

Vol 121 (2) ◽

pp. 418-426 ◽

Cited By ~ 18

Author(s):

Eva Berlot ◽

George Prichard ◽

Jill O’Reilly ◽

Naveed Ejaz ◽

Jörn Diedrichsen

Keyword(s):

Sensorimotor Cortex ◽

High Field ◽

Sensory Input ◽

Brain Activity ◽

Activity Patterns ◽

Sensory Information ◽

Sensory Stimulation ◽

Active Movement ◽

Contralateral Hemisphere ◽

Ipsilateral Hemisphere

Hand and finger movements are mostly controlled through crossed corticospinal projections from the contralateral hemisphere. During unimanual movements, activity in the contralateral hemisphere is increased while the ipsilateral hemisphere is suppressed below resting baseline. Despite this suppression, unimanual movements can be decoded from ipsilateral activity alone. This indicates that ipsilateral activity patterns represent parameters of ongoing movement, but the origin and functional relevance of these representations is unclear. In this study, we asked whether ipsilateral representations are caused by active movement or whether they are driven by sensory input. Participants alternated between performing single finger presses and having fingers passively stimulated while we recorded brain activity using high-field (7T) functional imaging. We contrasted active and passive finger representations in sensorimotor areas of ipsilateral and contralateral hemispheres. Finger representations in the contralateral hemisphere were equally strong under passive and active conditions, highlighting the importance of sensory information in feedback control. In contrast, ipsilateral finger representations in the sensorimotor cortex were stronger during active presses. Furthermore, the spatial distribution of finger representations differed between hemispheres: the contralateral hemisphere showed the strongest finger representations in Brodmann areas 3a and 3b, whereas the ipsilateral hemisphere exhibited stronger representations in premotor and parietal areas. Altogether, our results suggest that finger representations in the two hemispheres have different origins: contralateral representations are driven by both active movement and sensory stimulation, whereas ipsilateral representations are mainly engaged during active movement. NEW & NOTEWORTHY Movements of the human body are mostly controlled by contralateral cortical regions. The function of ipsilateral activity during movements remains elusive. Using high-field neuroimaging, we investigated how human contralateral and ipsilateral hemispheres represent active and passive finger presses. We found that representations in contralateral sensorimotor cortex are equally strong during both conditions. Ipsilateral representations were mostly present during active movement, suggesting that sensorimotor areas do not receive direct sensory input from the ipsilateral hand.

Download Full-text

Higher-order thalamocortical inputs gate synaptic long-term potentiation via disinhibition

10.1101/281477 ◽

2018 ◽

Cited By ~ 3

Author(s):

Leena E. Williams ◽

Anthony Holtmaat

Keyword(s):

Pyramidal Neurons ◽

Sensory Information ◽

Long Term Potentiation ◽

Higher Order ◽

Synaptic Circuits ◽

Term Potentiation ◽

Cortical Pyramidal Neurons ◽

Whisker Stimulation ◽

Synaptic Circuitry

SUMMARYSensory experience and perceptual learning changes the receptive field properties of cortical pyramidal neurons, largely mediated by long-term potentiation (LTP) of synapses. The circuit mechanisms underlying cortical LTP remain unclear. In the mouse somatosensory cortex (S1), LTP can be elicited in layer (L) 2/3 pyramidal neurons by rhythmic whisker stimulation. We combined electrophysiology, optogenetics, and chemogenetics in thalamocortical slices to dissect the synaptic circuitry underlying this LTP. We found that projections from higher-order, posteriormedial thalamic complex (POm) to S1 are key to eliciting NMDAR-dependent LTP of intracortical synapses. Paired activation of intracortical and higher-order thalamocortical pathways increased vasoactive intestinal peptide (VIP) interneuron and decreased somatostatin (SST) interneuron activity, which was critical for inducing LTP. Our results reveal a novel circuit motif in which higher-order thalamic feedback gates plasticity of intracortical synapses in S1 via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information.

Download Full-text

The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2009.0073 ◽

2009 ◽

Vol 364 (1529) ◽

pp. 2565-2576 ◽

Cited By ~ 2

Author(s):

S. Kasparov ◽

A. G. Teschemacher

Keyword(s):

Viral Vectors ◽

Pyramidal Neurons ◽

Viral Gene ◽

Volume Transmission ◽

Neuronal Populations ◽

Central Neurons ◽

Wide Range ◽

Cortical Pyramidal Neurons ◽

The Brain

In contrast to some other neuronal populations, for example hippocampal or cortical pyramidal neurons, mechanisms of synaptic integration and transmitter release in central neurons that contain noradrenaline (NA) and serotonin (5HT) are not well understood. These cells, crucial for a wide range of autonomic and behavioural processes, have long un-myelinated axons with hundreds of varicosities where transmitters are synthesized and released. Both seem to signal mostly in ‘volume transmission’ mode. Very little is known about the rules that apply to this type of transmission in the brain and the factors that regulate the release of NA and 5HT. We discuss some of our published studies and more recent experiments in which viral vectors were used to investigate the physiology of these neuronal populations. We also focus on currently unresolved issues concerning the mechanism of volume transmission by NA and 5HT in the brain. We suggest that clarifying the role of astroglia in this process could be essential for our understanding of central noradrenergic and 5HT signalling.

Download Full-text

Relation Between Level of Prefrontal Activity and Subject's Performance

Journal of Psychophysiology ◽

10.1027//0269-8803.13.2.117 ◽

1999 ◽

Vol 13 (2) ◽

pp. 117-125 ◽

Cited By ~ 14

Author(s):

Laurence Casini ◽

Françoise Macar ◽

Marie-Hélène Giard

Keyword(s):

Brain Activity ◽

Sensory Information ◽

Practice Phase ◽

Trained Subjects ◽

Anagram Task ◽

Economic Information ◽

Long Duration ◽

Level Of Activity ◽

The Brain ◽

Processing Mechanism

Abstract The experiment reported here was aimed at determining whether the level of brain activity can be related to performance in trained subjects. Two tasks were compared: a temporal and a linguistic task. An array of four letters appeared on a screen. In the temporal task, subjects had to decide whether the letters remained on the screen for a short or a long duration as learned in a practice phase. In the linguistic task, they had to determine whether the four letters could form a word or not (anagram task). These tasks allowed us to compare the level of brain activity obtained in correct and incorrect responses. The current density measures recorded over prefrontal areas showed a relationship between the performance and the level of activity in the temporal task only. The level of activity obtained with correct responses was lower than that obtained with incorrect responses. This suggests that a good temporal performance could be the result of an efficacious, but economic, information-processing mechanism in the brain. In addition, the absence of this relation in the anagram task results in the question of whether this relation is specific to the processing of sensory information only.

Download Full-text

Understanding Emotions: Origins and Roles of the Amygdala

Biomolecules ◽

10.3390/biom11060823 ◽

2021 ◽

Vol 11 (6) ◽

pp. 823

Author(s):

Goran Šimić ◽

Mladenka Tkalčić ◽

Vana Vukić ◽

Damir Mulc ◽

Ena Španić ◽

...

Keyword(s):

Sensory Information ◽

Anterior Cingulate ◽

Central Nucleus ◽

Subcortical Structures ◽

Neuronal Populations ◽

Efferent Projections ◽

Short And Long Term ◽

Understanding Emotions ◽

Fight Or Flight Response ◽

And Behavior

Emotions arise from activations of specialized neuronal populations in several parts of the cerebral cortex, notably the anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as the amygdala, ventral striatum, putamen, caudate nucleus, and ventral tegmental area. Feelings are conscious, emotional experiences of these activations that contribute to neuronal networks mediating thoughts, language, and behavior, thus enhancing the ability to predict, learn, and reappraise stimuli and situations in the environment based on previous experiences. Contemporary theories of emotion converge around the key role of the amygdala as the central subcortical emotional brain structure that constantly evaluates and integrates a variety of sensory information from the surroundings and assigns them appropriate values of emotional dimensions, such as valence, intensity, and approachability. The amygdala participates in the regulation of autonomic and endocrine functions, decision-making and adaptations of instinctive and motivational behaviors to changes in the environment through implicit associative learning, changes in short- and long-term synaptic plasticity, and activation of the fight-or-flight response via efferent projections from its central nucleus to cortical and subcortical structures.

Download Full-text