Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice

AbstractFrontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood. Chemogenetic suppression of top-down neuron activity selectively during adolescence, but not later periods, produces long-lasting visual attentional behavior deficits, and results in excessive loss of local excitatory inputs in adulthood. Our study reveals an adolescent sensitive period when top-down neurons integrate local circuits with long-range connectivity to produce attentional behavior.

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Supersaturation of VEP in Migraine without Aura Patients Treated with Topiramate: An Anatomo-Functional Biomarker of the Disease

Journal of Clinical Medicine ◽

10.3390/jcm10040769 ◽

2021 ◽

Vol 10 (4) ◽

pp. 769

Author(s):

Ciro De Luca ◽

Sara Gori ◽

Sonia Mazzucchi ◽

Elisa Dini ◽

Martina Cafalli ◽

...

Keyword(s):

Visual Cortex ◽

Cortical Neurons ◽

Migraine Without Aura ◽

Inverse Correlation ◽

Primary Headache ◽

Contrast Gain ◽

High Prevalence ◽

Functional Pathway ◽

Inhibitory Signaling ◽

Potential Use

Migraine is a primary headache with high prevalence among the general population, characterized by functional hypersensitivity to both exogenous and endogenous stimuli particularly affecting the nociceptive system. The hyperresponsivity of cortical neurons could be due to a disequilibrium in the excitatory/inhibitory signaling. This study aimed to investigate the anatomo-functional pathway from the retina to the primary visual cortex using visual evoked potentials (VEP). Contrast gain protocol was used in 15 patients diagnosed with migraine without aura (at baseline and after 3 months of topiramate therapy) and 13 controls. A saturation (S) index was assessed to monitor the response of VEP’s amplitude to contrast gain. Non-linear nor monotone growth of VEP (S < 0.95) was defined as supersaturation. A greater percentage of migraine patients (53%) relative to controls (7%) showed this characteristic. A strong inverse correlation was found between the S index and the number of days separating the registration of VEP from the next migraine attack. Moreover, allodynia measured through the Allodynia Symptoms Check-list (ASC-12) correlates with the S index both at baseline and after 3 months of topiramate treatment. Other clinical characteristics were not related to supersaturation. Topiramate therapy, although effective, did not influence electrophysiological parameters suggesting a non-intracortical nor retinal origin of the supersaturation (with possible involvement of relay cells from the lateral geniculate nucleus). In conclusion, the elaboration of visual stimuli and visual cortex activity is different in migraine patients compared to controls. More data are necessary to confirm the potential use of the S index as a biomarker for the migraine cycle (association with the pain-phase) and cortical sensitization (allodynia).

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Neuronal Distribution Across the Cerebral Cortex of the Marmoset Monkey (Callithrix jacchus)

Cerebral Cortex ◽

10.1093/cercor/bhy263 ◽

2018 ◽

Vol 29 (9) ◽

pp. 3836-3863 ◽

Cited By ~ 10

Author(s):

Nafiseh Atapour ◽

Piotr Majka ◽

Ianina H Wolkowicz ◽

Daria Malamanova ◽

Katrina H Worthy ◽

...

Keyword(s):

Cerebral Cortex ◽

Visual Cortex ◽

Complex Interaction ◽

Anterior Cingulate ◽

Functional Requirements ◽

Anterior Cortex ◽

Neuronal Density ◽

Marmoset Monkey ◽

Posterior Parietal ◽

Neuronal Distribution

Abstract Using stereological analysis of NeuN-stained sections, we investigated neuronal density and number of neurons per column throughout the marmoset cortex. Estimates of mean neuronal density encompassed a greater than 3-fold range, from >150 000 neurons/mm3 in the primary visual cortex to ~50 000 neurons/mm3 in the piriform complex. There was a trend for density to decrease from posterior to anterior cortex, but also local gradients, which resulted in a complex pattern; for example, in frontal, auditory, and somatosensory cortex neuronal density tended to increase towards anterior areas. Anterior cingulate, motor, premotor, insular, and ventral temporal areas were characterized by relatively low neuronal densities. Analysis across the depth of the cortex revealed greater laminar variation of neuronal density in occipital, parietal, and inferior temporal areas, in comparison with other regions. Moreover, differences between areas were more pronounced in the supragranular layers than in infragranular layers. Calculations of the number of neurons per unit column revealed a pattern that was distinct from that of neuronal density, including local peaks in the posterior parietal, superior temporal, precuneate, frontopolar, and temporopolar regions. These results suggest that neuronal distribution in adult cortex result from a complex interaction of developmental/ evolutionary determinants and functional requirements.

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Astrocytic modulation of information processing by layer 5 pyramidal neurons of the mouse visual cortex

10.1101/2020.07.09.190777 ◽

2020 ◽

Cited By ~ 2

Author(s):

Dimitri Ryczko ◽

Maroua Hanini-Daoud ◽

Steven Condamine ◽

Benjamin J. B. Bréant ◽

Maxime Fougère ◽

...

Keyword(s):

Visual Cortex ◽

Cortical Neurons ◽

Calcium Binding ◽

Pyramidal Neurons ◽

Binding Protein ◽

Contextual Information ◽

Dendritic Tree ◽

Cortical Layer ◽

List Type ◽

Ionic Environment

AbstractThe most complex cerebral functions are performed by the cortex which most important output is carried out by its layer 5 pyramidal neurons. Their firing reflects integration of sensory and contextual information that they receive. There is evidence that astrocytes influence cortical neurons firing through the release of gliotransmitters such as ATP, glutamate or GABA. These effects were described at the network and at the synaptic levels, but it is still unclear how astrocytes influence neurons input-output transfer function at the cellular level. Here, we used optogenetic tools coupled with electrophysiological, imaging and anatomical approaches to test whether and how astrocytic activation affected processing and integration of distal inputs to layer 5 pyramidal neurons (L5PN). We show that optogenetic activation of astrocytes near L5PN cell body prolonged firing induced by distal inputs to L5PN and potentiated their ability to trigger spikes. The observed astrocytic effects on L5PN firing involved glutamatergic transmission to some extent but relied on release of S100β, an astrocytic Ca2+-binding protein that decreases extracellular Ca2+ once released. This astrocyte-evoked decrease of extracellular Ca2+ elicited firing mediated by activation of Nav1.6 channels. Our findings suggest that astrocytes contribute to the cortical fundamental computational operations by controlling the extracellular ionic environment.Key Points SummaryIntegration of inputs along the dendritic tree of layer 5 pyramidal neurons is an essential operation as these cells represent the most important output carrier of the cerebral cortex. However, the contribution of astrocytes, a type of glial cell to these operations is poorly documented.Here we found that optogenetic activation of astrocytes in the vicinity of layer 5 in the mouse primary visual cortex induce spiking in local pyramidal neurons through Nav1.6 ion channels and prolongs the responses elicited in these neurons by stimulation of their distal inputs in cortical layer 1.This effect partially involved glutamatergic signalling but relied mostly on the astrocytic calcium-binding protein S100β, which regulates the concentration of calcium in the extracellular space around neurons.These findings show that astrocytes contribute to the fundamental computational operations of the cortex by acting on the ionic environment of neurons.

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The Development of Active Binocular Vision under Normal and Alternate Rearing Conditions

10.1101/2020.02.20.957449 ◽

2020 ◽

Author(s):

Lukas Klimmasch ◽

Johann Schneider ◽

Alexander Lelais ◽

Bertram E. Shi ◽

Jochen Triesch

Keyword(s):

Visual Cortex ◽

Binocular Vision ◽

Cortical Neurons ◽

Orientation Tuning ◽

Active Perception ◽

Efficient Coding ◽

Rearing Conditions ◽

Active Binocular Vision ◽

Experimental Findings ◽

Visual Cortical

AbstractThe development of binocular vision is an active learning process comprising the development of disparity tuned neurons in visual cortex and the establishment of precise vergence control of the eyes. We present a computational model for the learning and self-calibration of active binocular vision based on the Active Efficient Coding framework, an extension of classic efficient coding ideas to active perception. Under normal rearing conditions, the model develops disparity tuned neurons and precise vergence control, allowing it to correctly interpret random dot stereogramms. Under altered rearing conditions modeled after neurophysiological experiments, the model qualitatively reproduces key experimental findings on changes in binocularity and disparity tuning. Furthermore, the model makes testable predictions regarding how altered rearing conditions impede the learning of precise vergence control. Finally, the model predicts a surprising new effect that impaired vergence control affects the statistics of orientation tuning in visual cortical neurons.

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Perinatal fentanyl exposure leads to long-lasting impairments in somatosensory circuit function and behavior

10.1101/2020.09.19.304352 ◽

2020 ◽

Author(s):

Jason Alipio ◽

Catherine Haga ◽

Megan E Fox ◽

Keiko Arakawa ◽

Rakshita Balaji ◽

...

Keyword(s):

Cortical Neurons ◽

Morphological Changes ◽

Anterior Cingulate ◽

Preclinical Model ◽

Sensory Stimuli ◽

Synaptic Excitation ◽

Molecular Abnormalities ◽

Postsynaptic Currents ◽

And Behavior

One consequence of the opioid epidemic are lasting neurodevelopmental sequelae afflicting adolescents exposed to opioids in the womb. A translationally relevant and developmentally accurate preclinical model is needed to understand the behavioral, circuit, network, and molecular abnormalities resulting from this exposure. By employing a novel preclinical model of perinatal fentanyl exposure, our data reveal that fentanyl has several dose-dependent, developmental consequences to somatosensory function and behavior. Newborn male and female mice exhibit signs of withdrawal and sensory-related deficits that extend at least to adolescence. As fentanyl exposure does not affect dams' health or maternal behavior, these effects result from the direct actions of perinatal fentanyl on the pups' developing brain. At adolescence, exposed mice exhibit reduced adaptation to sensory stimuli, and a corresponding impairment in primary somatosensory (S1) function. In vitro electrophysiology demonstrates a long-lasting reduction in S1 synaptic excitation, evidenced by decreases in release probability, NMDA receptor-mediated postsynaptic currents, and frequency of miniature excitatory postsynaptic currents, as well as increased frequency of miniature inhibitory postsynaptic currents. In contrast, anterior cingulate cortical neurons exhibit an opposite phenotype, with increased synaptic excitation. Consistent with these changes, electrocorticograms reveal suppressed ketamine-evoked γ oscillations. Morphological analysis of S1 pyramidal neurons indicate reduced dendritic complexity, dendritic length, and soma size. Further, exposed mice exhibited abnormal cortical mRNA expression of key receptors and neuronal growth and development, changes that were consistent with the electrophysiological and morphological changes. These findings demonstrate the lasting sequelae of perinatal fentanyl exposure on sensory processing and function.

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Two movement-related foci in the primate cingulate cortex observed in signal-triggered and self-paced forelimb movements

Journal of Neurophysiology ◽

10.1152/jn.1991.65.2.188 ◽

1991 ◽

Vol 65 (2) ◽

pp. 188-202 ◽

Cited By ~ 219

Author(s):

K. Shima ◽

K. Aya ◽

H. Mushiake ◽

M. Inase ◽

H. Aizawa ◽

...

Keyword(s):

Cortical Neurons ◽

Primary Motor Cortex ◽

Motor Task ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

The Self ◽

Anterior Cingulate ◽

Key Press ◽

Flexor Muscles ◽

Hrp Method

1. Single-unit activity in the cingulate cortex of the monkey was recorded during the performance of sensorially (visual, auditory, or tactile) triggered or self-paced forelimb key press movements. 2. Microelectrodes were inserted into the broad rostrocaudal expanse of the cingulate cortex, including the upper and lower banks of the cingulate sulcus and the hemispheric medial wall of the cingulate gyrus. 3. A total of 1,042 task-related neurons were examined, the majority of which were related to the execution of the key press movements. In greater than 60% of them, the movement-related activity preceded the activity in the distal flexor muscles. 4. The movement-related neurons were distributed, in two foci, in the posterior and anterior parts of the cingulate cortex, both including the upper and lower banks of the cingulate sulcus. The posterior focus was found to largely overlap the area projecting to the forelimb area of the primary motor cortex by the use of the horseradish peroxidase (HRP) method. 5. About 40% of the cingulate cortical neurons showed equimagnitude responses during the signal-triggered and self-paced movements. The neurons exhibiting a selective or differential response to the self-paced motor task were more frequently observed in the anterior than in the posterior cingulate cortex. 6. The long-lead type of changes in activity, ranging from 500 ms to 2 s, were observed mainly before the self-paced and, much less frequently, before the triggered movements. They were particularly abundant in the anterior cingulate cortex. 7. Only a few of the neurons showed activity time-locked to the onset of the sensory signals. 8. These observations indicate that the anterior and posterior parts of the cingulate cortex are distinct entities participating in the performance of limb movements, even if the movements are simple, such as those in this study.

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Postnatal Development of Onset Transient Responses in Macaque V1 and V2 Neurons

Journal of Neurophysiology ◽

10.1152/jn.90446.2008 ◽

2008 ◽

Vol 100 (3) ◽

pp. 1476-1487 ◽

Cited By ~ 11

Author(s):

Bin Zhang ◽

Earl L. Smith ◽

Yuzo M. Chino

Keyword(s):

Visual Cortex ◽

Eye Movements ◽

Primary Visual Cortex ◽

Cortical Neurons ◽

Newborn Infants ◽

Neuronal Firing ◽

Transient Responses ◽

Visual Cortical ◽

Better Than

Vision of newborn infants is limited by immaturities in their visual brain. In adult primates, the transient onset discharges of visual cortical neurons are thought to be intimately involved with capturing the rapid succession of brief images in visual scenes. Here we sought to determine the responsiveness and quality of transient responses in individual neurons of the primary visual cortex (V1) and visual area 2 (V2) of infant monkeys. We show that the transient component of neuronal firing to 640-ms stationary gratings was as robust and as reliable as in adults only 2 wk after birth, whereas the sustained component was more sluggish in infants than in adults. Thus the cortical circuitry supporting onset transient responses is functionally mature near birth, and our findings predict that neonates, known for their “impoverished vision,” are capable of initiating relatively mature fixating eye movements and of performing in detection of simple objects far better than traditionally thought.

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Cortical Mechanisms for Emotional Fear and Chronic Pain

European Psychiatry ◽

10.1016/s0924-9338(09)70318-9 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

M. Zhuo

Keyword(s):

Chronic Pain ◽

Emotional Disorders ◽

Cortical Neurons ◽

Neural Mechanism ◽

Anterior Cingulate ◽

Cellular Mechanisms ◽

New Genes ◽

Trace Fear ◽

The Brain ◽

Synaptic Model

Investigation of molecular and cellular mechanisms of synaptic plasticity is the major focus of many neuroscientists. There are two major reasons for searching new genes and molecules contributing to central plasticity: first, it provides basic neural mechanism for learning and memory, a key function of the brain; second, it provides new targets for treating brain-related disease. Here, I propose that LTP in the anterior cingulate cortex (ACC) as a synaptic model for emotional fear and chronic pain in the brain. Integrative approaches including genetic, neurobiological and physiological methods are used to investigate the roles of cortical neurons and microglia in synaptic LTP, fear and chronic pain. We have identified several key calcium-stimulated signaling molecules including AC1, CaMKIV and FMRP for AMPA receptor mediated cingulate LTP, trace fear memory, and chronic pain. By contrast, microglia only contributes to changes in spinal dorsal horn, but not in the cortex. Our findings strongly suggest that ACC LTP may serve as a cellular model for studying central sensitization that related to fear and chronic pain, as well as pain-related cognitive emotional disorders.

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Temporal Integration by Stochastic Recurrent Network Dynamics With Bimodal Neurons

Journal of Neurophysiology ◽

10.1152/jn.01100.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 3859-3867 ◽

Cited By ~ 27

Author(s):

Hiroshi Okamoto ◽

Yoshikazu Isomura ◽

Masahiko Takada ◽

Tomoki Fukai

Keyword(s):

Cortical Neurons ◽

Cognitive Task ◽

Temporal Integration ◽

Activity Patterns ◽

Recurrent Network ◽

External Input ◽

Delay Period ◽

Anterior Cingulate ◽

Population Activity ◽

The Individual

Temporal integration of externally or internally driven information is required for a variety of cognitive processes. This computation is generally linked with graded rate changes in cortical neurons, which typically appear during a delay period of cognitive task in the prefrontal and other cortical areas. Here, we present a neural network model to produce graded (climbing or descending) neuronal activity. Model neurons are interconnected randomly by AMPA-receptor–mediated fast excitatory synapses and are subject to noisy background excitatory and inhibitory synaptic inputs. In each neuron, a prolonged afterdepolarizing potential follows every spike generation. Then, driven by an external input, the individual neurons display bimodal rate changes between a baseline state and an elevated firing state, with the latter being sustained by regenerated afterdepolarizing potentials. When the variance of background input and the uniform weight of recurrent synapses are adequately tuned, we show that stochastic noise and reverberating synaptic input organize these bimodal changes into a sequence that exhibits graded population activity with a nearly constant slope. To test the validity of the proposed mechanism, we analyzed the graded activity of anterior cingulate cortex neurons in monkeys performing delayed conditional Go/No-go discrimination tasks. The delay-period activities of cingulate neurons exhibited bimodal activity patterns and trial-to-trial variability that are similar to those predicted by the proposed model.

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