scholarly journals An analog of psychedelics restores functional neural circuits disrupted by unpredictable stress

2021 ◽  
Author(s):  
Ju Lu ◽  
Michelle Tjia ◽  
Brian Mullen ◽  
Bing Cao ◽  
Kacper Lukasiewicz ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Sensory Processing ◽  
Cognitive Deficits ◽  
Neural Circuits ◽  
Wide Spectrum ◽  
Activity Patterns ◽  
Mild Stress ◽  
Brain Functions ◽  
Post Stress

AbstractPsychological stress affects a wide spectrum of brain functions and poses risks for many mental disorders. However, effective therapeutics to alleviate or revert its deleterious effects are lacking. A recently synthesized psychedelic analog tabernanthalog (TBG) has demonstrated anti-addictive and antidepressant potential. Whether TBG can rescue stress-induced affective, sensory, and cognitive deficits, and how it may achieve such effects by modulating neural circuits, remain unknown. Here we show that in mice exposed to unpredictable mild stress (UMS), administration of a single dose of TBG decreases their anxiety level and rescues deficits in sensory processing as well as in cognitive flexibility. Post-stress TBG treatment promotes the regrowth of excitatory neuron dendritic spines lost during UMS, decreases the baseline neuronal activity, and enhances whisking-modulation of neuronal activity in the somatosensory cortex. Moreover, calcium imaging in head-fixed mice performing a whisker-dependent texture discrimination task shows that novel textures elicit responses from a greater proportion of neurons in the somatosensory cortex than do familiar textures. Such differential response is diminished by UMS and is restored by TBG. Together, our study reveals the effects of UMS on cortical neuronal circuit activity patterns and demonstrate that TBG combats the detrimental effects of stress by modulating basal and stimulus-dependent neural activity in cortical networks.

Neuronal Activity in Somatosensory Cortex of Monkeys Using a Precision Grip. III. Responses to Altered Friction Perturbations

1999 ◽  
Vol 81 (2) ◽  
pp. 845-857 ◽  
Author(s):  
Iran Salimi ◽  
Thomas Brochier ◽  
Allan M. Smith
Keyword(s):  
Somatosensory Cortex ◽  
Metal Surface ◽  
Neuronal Activity ◽  
Surface Coating ◽  
Activity Patterns ◽  
Precision Grip ◽  
Skin Surface ◽  
Load Force ◽  
Surface Load ◽  
Petroleum Jelly

Neuronal activity in somatosensory cortex of monkeys using a precision grip. III. Responses to altered friction perturbations. The purpose of this investigation was to examine the activity changes in single units of the somatosensory cortex in response to lubricating and adhesive coatings applied to a hand-held object. Three monkeys were trained to grasp an object between the thumb and index fingers and to lift and hold it stationary within a narrow position window for 1 s before release. Grip forces normal to the skin surface, load forces tangential to the skin surface, and the displacement of the object were measured on each trial. Adhesive (rosin) and lubricant (petroleum jelly) coatings were applied to the smooth metal surface of the object to alter the friction against the skin. In addition, neuronal activity evoked by force pulse-perturbations generating shear forces and slip on the skin were compared with the patterns of activity elicited by grasping and lifting the coated surfaces. Following changes in surface coatings, both monkeys modulated the rate at which grip forces normal to the skin surface and load forces tangential to the skin surface were applied during the lifting phase of the task. As a result, the ratio of the rates of change of the two forces was proportionately scaled to the surface coating properties with the more slippery surfaces, having higher ratios. This precise control of normal and tangential forces enabled the monkeys to generate adequate grip forces and prevent slip of the object. From a total of 386 single neurons recorded in the hand area of the somatosensory cortex, 92 were tested with at least 1 coating. Cell discharge changed significantly with changes in surface coating in 62 (67%) of these cells. Of these coating-related cells, 51 were tested with both an adhesive and lubricating coating, and 45 showed significant differences in activity between the untreated metal surface and either the lubricant or the adhesive coating. These cells were divided into three main groups on the basis of their response patterns. In the first group ( group A), the peak discharge increased significantly when the grasped surface was covered with lubricant. These cells appeared to be selectively sensitive to slip of the object on the skin. The second group ( group B) was less activated by the adhesive surface compared with either the untreated metal or the lubricated surface, and they responded mainly to variations in the force normal to the skin surface. These cells provide useful feedback for the control of grip force. The third group ( group C) responded to both slips and to changes in forces tangential to the skin. Most of these cells responded with a biphasic pattern reflecting the bidirectional changes in load force as the object was first accelerated and then decelerated. One hundred sixty-eight of the 386 isolated neurons were tested with brief perturbations during the task. Of these, 147 (88%) responded to the perturbation with a significant change in activity. In most of the cells, the response to the perturbation was shorter than 100 ms with a mean latency of 44.1 ± 16.3 (SD) ms. For each of the cell groups, the activity patterns triggered by the perturbations were consistent with the activity patterns generated during the grasping and lifting of the coated object.

scholarly journals Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target

2021 ◽  
Vol 7 (12) ◽  
pp. eabd8261
Author(s):  
Takuya Okada ◽  
Daisuke Kato ◽  
Yuki Nomura ◽  
Norihiko Obata ◽  
Xiangyu Quan ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Inflammatory Pain ◽  
Neuronal Excitability ◽  
Activity Patterns ◽  
Neuron Activity ◽  
Cellular Mechanisms ◽  
Pain Models ◽  
Voltage Dependent

Sustained neuropathic pain from injury or inflammation remains a major burden for society. Rodent pain models have informed some cellular mechanisms increasing neuronal excitability within the spinal cord and primary somatosensory cortex (S1), but how activity patterns within these circuits change during pain remains unclear. We have applied multiphoton in vivo imaging and holographic stimulation to examine single S1 neuron activity patterns and connectivity during sustained pain. Following pain induction, there is an increase in synchronized neuronal activity and connectivity within S1, indicating the formation of pain circuits. Artificially increasing neuronal activity and synchrony using DREADDs reduced pain thresholds. The expression of N-type voltage-dependent Ca2+ channel subunits in S1 was increased after pain induction, and locally blocking these channels reduced both the synchrony and allodynia associated with inflammatory pain. Targeting these S1 pain circuits, via inhibiting N-type Ca2+ channels or other approaches, may provide ways to reduce inflammatory pain.

Altered somatosensory cortex neuronal activity in a rat model of Parkinson's disease and levodopa-induced dyskinesias

2017 ◽  
Vol 294 ◽  
pp. 19-31 ◽  
Author(s):  
Mesbah Alam ◽  
Regina Rumpel ◽  
Xingxing Jin ◽  
Christof von Wrangel ◽  
Sarah K. Tschirner ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Somatosensory Cortex ◽  
Neuronal Activity ◽  
Rat Model

scholarly journals Epileptogenesis due to glia-mediated synaptic scaling

2008 ◽  
Vol 6 (37) ◽  
pp. 655-668 ◽  
Author(s):  
Cristina Savin ◽  
Jochen Triesch ◽  
Michael Meyer-Hermann
Keyword(s):  
Immune System ◽  
Neuronal Activity ◽  
Activity Patterns ◽  
Brain Inflammation ◽  
Network Activity ◽  
Homeostatic Regulation ◽  
Synaptic Scaling ◽  
Tnf Α ◽  
Factor Α ◽  
Potential Interactions

Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.

scholarly journals ApoE4 attenuates cortical neuronal activity and impairs memory in young apoE4 rats

2021 ◽  
Author(s):  
Ilona Har-Paz ◽  
Elor Arieli ◽  
Anan Moran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Neuronal Activity ◽  
Genetic Risk ◽  
Cortical Neurons ◽  
Late Onset ◽  
Genetic Risk Factor ◽  
Normal Brain ◽  
Brain Functions

AbstractThe E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD related neuropathology. Understanding these primary dysfunctions is vital for early detection of AD and the development of therapeutic strategies for it. Recently we have shown impaired extra-hippocampal memory in young apoE4 mice – a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we test the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 and wildtype rats, before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young apoE4 rats showed impaired CTA learning, consistent with our previous results in apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Single neuron and ensemble analyses of taste coding demonstrated that apoE4 neurons could be used to correctly classify tastes, but were unable to undergo plasticity to support learning. Our results suggest that apoE4 impacts brain excitability and plasticity early in life and may act as an initiator for later AD pathologies.Significant statementThe ApoE4 allele is the strongest genetic risk-factor for late-onset Alzheimer’s disease (AD), yet the link between apoE4 and AD is still unclear. Recent molecular and in-vitro studies suggest that apoE4 interferes with normal brain functions decades before the development of its related AD neuropathology. Here we recorded the activity of cortical neurons from young apoE4 rats during extra-hippocampal learning to study early apoE4 neuronal activity abnormalities, and their effects over coding capacities. We show that apoE4 drastically reduces basal and stimuli-evoked cortical activity in both excitatory and inhibitory neurons. The apoE4-induced activity attenuation did not prevent coding of stimuli identity and valence, but impaired capacity to undergo activity changes to support learning. Our findings support the hypothesis that apoE4 interfere with normal neuronal plasticity early in life; a deficit that may lead to late-onset AD development.

scholarly journals Recurrent circuitry is required to stabilize piriform cortex odor representations across brain states

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kevin A Bolding ◽  
Shivathmihai Nagappan ◽  
Bao-Xia Han ◽  
Fan Wang ◽  
Kevin M Franks
Keyword(s):  
Neural Activity ◽  
Neural Circuits ◽  
Activity Patterns ◽  
Piriform Cortex ◽  
Theoretical Studies ◽  
Pattern Completion ◽  
Attractor Networks ◽  
Attractor Dynamics ◽  
Brain States ◽  
Associative Function

Pattern completion, or the ability to retrieve stable neural activity patterns from noisy or partial cues, is a fundamental feature of memory. Theoretical studies indicate that recurrently connected auto-associative or discrete attractor networks can perform this process. Although pattern completion and attractor dynamics have been observed in various recurrent neural circuits, the role recurrent circuitry plays in implementing these processes remains unclear. In recordings from head-fixed mice, we found that odor responses in olfactory bulb degrade under ketamine/xylazine anesthesia while responses immediately downstream, in piriform cortex, remain robust. Recurrent connections are required to stabilize cortical odor representations across states. Moreover, piriform odor representations exhibit attractor dynamics, both within and across trials, and these are also abolished when recurrent circuitry is eliminated. Here, we present converging evidence that recurrently-connected piriform populations stabilize sensory representations in response to degraded inputs, consistent with an auto-associative function for piriform cortex supported by recurrent circuitry.

scholarly journals Non-canonical role for Lpar1-EGFP subplate neurons in early postnatal mouse somatosensory cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Filippo Ghezzi ◽  
Andre Marques-Smith ◽  
Paul G Anastasiades ◽  
Daniel Lyngholm ◽  
Cristiana Vagnoni ◽  
...  
Keyword(s):  
Cell Death ◽  
Somatosensory Cortex ◽  
Sensory Processing ◽  
Marginal Zone ◽  
Time Window ◽  
Columnar Structure ◽  
Synaptic Connectivity ◽  
Thalamic Input ◽  
Subplate Neurons ◽  
Local Input

Subplate neurons (SPNs) are thought to play a role in nascent sensory processing in neocortex. To better understand how heterogeneity within this population relates to emergent function, we investigated the synaptic connectivity of Lpar1-EGFP SPNs through the first postnatal week in whisker somatosensory cortex (S1BF). These SPNs comprise of two morphological subtypes: fusiform SPNs with local axons, and pyramidal SPNs with axons that extend through the marginal zone. The former receive translaminar synaptic input up until the emergence of the whisker barrels; a timepoint coincident with significant cell death. In contrast, pyramidal SPNs receive local input from the subplate at early ages but then – during the later time window, acquire input from overlying cortex. Combined electrical and optogenetic activation of thalamic afferents identified that Lpar1-EGFP SPNs receive sparse thalamic innervation. These data reveal components of the postnatal network that interpret sparse thalamic input to direct the emergent columnar structure of S1BF.

scholarly journals Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Spontaneous Activity ◽  
Sensory Processing ◽  
Activity Patterns ◽  
Network Activity ◽  
Synaptic Connections ◽  
Pairwise Correlations ◽  
Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

Sign in / Sign up

Export Citation Format

Share Document