scholarly journals An unconventional GABAergic circuit differently controls pyramidal neuron activity in two visual cortical areas via endocannabinoids

2021 ◽  
Author(s):  
Martin Montmerle ◽  
Fani Koukouli ◽  
Andrea Aguirre ◽  
Jeremy Peixoto ◽  
Vikash Choudhary ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Cannabinoid Receptor ◽  
Gaba Release ◽  
Network Activity ◽  
Connectivity Pattern ◽  
Neuron Activity ◽  
Cortical Areas ◽  
Visual Cortical ◽  
And Function

Perisomatic inhibition of neocortical pyramidal neurons (PNs) coordinates cortical network activity during sensory processing, and it has been mainly attributed to parvalbumin-expressing basket cells (BCs). However, cannabinoid receptor type 1 (CB1)-expressing interneurons also inhibit the perisomatic region of PNs but the connectivity and function of these elusive, yet prominent, neocortical GABAergic cells is unknown. We found that the connectivity pattern of CB1-positive BCs strongly differs between primary and high-order cortical visual areas. Moreover, persistently active CB1 signaling suppresses GABA release from CB1 BCs in the medial secondary visual cortex (V2M), but not in the primary (V1) visual area. Accordingly, in vivo, tonic CB1 signaling is responsible for higher but less coordinated PN activity in V2M than in V1. Our results indicate a differential CB1-mediated mechanism controlling PN activity, and suggest an alternative connectivity schemes of a specific GABAergic circuit in different cortical areas

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals Homeostatic plasticity rules control the wiring of axo-axonic synapses at the axon initial segment

2018 ◽  
Author(s):  
Alejandro Pan-Vazquez ◽  
Winnie Wefelmeyer ◽  
Victoria Gonzalez Sabater ◽  
Juan Burrone
Keyword(s):  
Initial Segment ◽  
Pyramidal Cells ◽  
Axon Initial Segment ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Chandelier Cells ◽  
Local Circuits ◽  
And Function

AbstractGABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex1,2. However, the rules that govern the wiring of interneurons are not well understood3. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS)4. Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. In this study, we investigated the role of activity in the formation and plasticity of ChC synapses. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found that increases in the activity of either pyramidal cells or individual ChCs during this temporal window resulted in a reversible decrease in axo-axonic connections. Voltage imaging of GABAergic transmission at the AIS showed that axo-axonic synapses were depolarising during this period. Identical manipulations of network activity in older mice (P40-P46), when ChC synapses are inhibitory, resulted in an increase in axo-axonic synapses. We propose that the direction of ChC plasticity follows homeostatic rules that depend on the polarity of axo-axonic synapses.

Topographic organization, number, and laminar distribution of callosal cells connecting visual cortical areas 17 and 18 of normally pigmented and Siamese cats

1992 ◽  
Vol 9 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Nancy E. J. Berman ◽  
Simon Grant
Keyword(s):  
Pyramidal Neurons ◽  
Area 17 ◽  
Vertical Meridian ◽  
Cortical Areas ◽  
Area Centralis ◽  
Areas 17 And 18 ◽  
Contralateral Eye ◽  
Visual Cortical ◽  
Callosal Pathway ◽  
Cell Zone

AbstractThe callosal connections between visual cortical areas 17 and 18 in adult normally pigmented and “Boston” Siamese cats were studied using degeneration methods, and by transport of WGA-HRP combined with electrophysiological mapping. In normal cats, over 90% of callosal neurons were located in the supragranular layers. The supragranular callosal cell zone spanned the area 17/18 border and extended, on average, some 2–3 mm into both areas to occupy a territory which was roughly co-extensive with the distribution of callosal terminations in these areas. The region of the visual field adjoining the vertical meridian that was represented by neurons in the supragranular callosal cell zone was shown to increase systematically with decreasing visual elevation. Thus, close to the area centralis, receptive-field centers recorded from within this zone extended only up to 5 deg into the contralateral hemifield but at elevations of -10 deg and -40 deg they extended as far as 8 deg and 14 deg, respectively, into this hemifield. This suggests an element of visual non-correspondence in the callosal pathway between these cortical areas, which may be an essential substrate for “coarse” stereopsis at the visual midline.In the Siamese cats, the callosal cell and termination zones in areas 17 and 18 were expanded in width compared to the normal animals, but the major components were less robust. The area 17/18 border was often devoid of callosal axons and, in particular, the number of supragranular layer neurons participating in the pathway were drastically reduced, to only about 25% of those found in the normally pigmented adults. The callosal zones contained representations of the contralateral and ipsilateral hemifields that were roughly mirror-symmetric about the vertical meridian, and both hemifield representations increased with decreasing visual elevation. The extent and severity of the anomalies observed were similar across individual cats, regardless of whether a strabismus was also present. The callosal pathway between these visual cortical areas in the Siamese cat has been considered “silent,” since nearly all neurons within its territory are activated only by the contralateral eye. The paucity of supragranular pyramidal neurons involved in the pathway may explain this silence.

scholarly journals Altered GABAA,slow Inhibition and Network Oscillations in Mice Lacking the GABAA Receptor β3 Subunit

2009 ◽  
Vol 102 (6) ◽  
pp. 3643-3655 ◽  
Author(s):  
Harald Hentschke ◽  
Claudia Benkwitz ◽  
Matthew I. Banks ◽  
Mark G. Perkins ◽  
Gregg E. Homanics ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Gamma Oscillations ◽  
Theta Oscillations ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Gabaergic Inhibition ◽  
Wild Type ◽  
Hippocampal Network

Phasic GABAergic inhibition in hippocampus and neocortex falls into two kinetically distinct categories, GABAA,fast and GABAA,slow. In hippocampal area CA1, GABAA,fast is generally believed to underlie gamma oscillations, whereas the contribution of GABAA,slow to hippocampal rhythms has been speculative. Hypothesizing that GABAA receptors containing the β3 subunit contribute to GABAA,slow inhibition and that slow inhibitory synapses control excitability as well as contribute to network rhythms, we investigated the consequences of this subunit's absence on synaptic inhibition and network function. In pyramidal neurons of GABAA receptor β3 subunit-deficient (β3−/−) mice, spontaneous GABAA,slow inhibitory postsynaptic currents (IPSCs) were much less frequent, and evoked GABAA,slow currents were much smaller than in wild-type mice. Fittingly, long-lasting recurrent inhibition of population spikes was less powerful in the mutant, indicating that receptors containing β3 subunits contribute substantially to GABAA,slow currents in pyramidal neurons. By contrast, slow inhibitory control of GABAA,fast-producing interneurons was unaffected in β3−/− mice. In vivo hippocampal network activity was markedly different in the two genotypes. In β3−/− mice, epileptiform activity was observed, and theta oscillations were weaker, slower, less regular and less well coordinated across laminae compared with wild-type mice, whereas gamma oscillations were weaker and faster. The amplitude modulation of gamma oscillations at theta frequency (“nesting”) was preserved but was less well coordinated with theta oscillations. With the caveat that seizure-induced changes in inhibitory circuits might have contributed to the changes observed in the mutant animals, our results point to a strong contribution of β3 subunits to slow GABAergic inhibition onto pyramidal neurons but not onto GABAA,fast -producing interneurons and support different roles for these slow inhibitory synapses in the generation and coordination of hippocampal network rhythms.

Endocannabinoids Mediate Rapid Retrograde Signaling At Interneuron → Pyramidal Neuron Synapses of the Neocortex

2003 ◽  
Vol 89 (4) ◽  
pp. 2334-2338 ◽  
Author(s):  
Joseph Trettel ◽  
Eric S. Levine
Keyword(s):  
Pyramidal Neurons ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Gaba Release ◽  
Inhibitory Interneurons ◽  
Strongly Correlated ◽  
Inhibitory Strength ◽  
Activity Dependent ◽  
Whole Cell Recordings

In the neocortex, inhibitory interneurons tightly regulate the firing patterns and integrative properties of pyramidal neurons (PNs). The endocannabinoid system of the neocortex may play an important role in the activity-dependent regulation of inhibitory (i.e., GABAergic) inputs received by PNs. In the present study, using whole cell recordings from layer 2/3 PNs in slices of mouse sensory cortex, we have identified a role for PN-derived endocannabinoids in the control of afferent inhibitory strength. Pairing evoked inhibitory currents with repeated epochs of postsynaptic depolarization led to a transient suppression of inhibition that was induced by a rise in postsynaptic Ca2+ and was expressed as a reduction in presynaptic GABA release. An antagonist (AM251) of the type-1 cannabinoid receptor blocked the depolarization-induced suppression of evoked inhibitory postsynaptic currents (eIPSCs), and the cannabinoid WIN55,212-2 reduced eIPSC amplitude and occluded suppression. The degree of WIN55,212-2-mediated inhibition of eIPSCs was strongly correlated with the magnitude of depolarization-induced suppression of the eIPSCs, suggesting that the WIN-sensitive afferents are suppressed by PN depolarization. Moreover, blocking endocannabinoid uptake with AM404 strongly modulated the kinetics and magnitude of eIPSC suppression. We conclude that the release of endocannabinoids from PNs allows for the postsynaptic control of presynaptic inhibition and could have profound consequences for the integrative properties of neocortical PNs.

scholarly journals Knock-down of hippocampal DISC1 in immune-challenged mice impairs the prefrontal-hippocampal coupling and the cognitive performance throughout development

2020 ◽  
Author(s):  
Xiaxia Xu ◽  
Lingzhen Song ◽  
Ileana L. Hanganu-Opatz
Keyword(s):  
Cognitive Impairment ◽  
Pyramidal Neurons ◽  
Behavioral Assessment ◽  
Network Activity ◽  
Whole Brain ◽  
Knock Down ◽  
Ca1 Pyramidal Neurons ◽  
Ca1 Area ◽  
Local Circuits

AbstractDisrupted-in-Schizophrenia 1 (DISC1) gene represents an intracellular hub of developmental processes and has been related to cognitive dysfunction in psychiatric disorders. Mice with whole-brain DISC1 knock-down show memory and executive deficits as result of impaired prefrontal-hippocampal communication throughout development, especially when combined with early environmental stressors, such as maternal immune activation (MIA). While synaptic dysfunction of layer 2/3 pyramidal neurons in neonatal prefrontal cortex (PFC) has been recently identified as one source of abnormal long-range coupling in these mice, it is still unclear whether the hippocampus (HP) is also compromised during development. Here we aim to fill this knowledge gap by combining in vivo electrophysiology and optogenetics with morphological and behavioral assessment of immune-challenged mice with DISC1 knock-down either in the whole brain (GE) or restricted to pyramidal neurons in CA1 area of intermediate/ventral HP (i/vHP) (GHPE). Both groups of mice show abnormal network activity, sharp-waves (SPWs) and neuronal firing in CA1 area. Moreover, optogenetic stimulation of CA1 pyramidal neurons fails to activate the local circuits in the neonatal PFC. These deficits that persist until pre-juvenile development are due to dendrite sparsification and loss of spines of CA1 pyramidal neurons. As a long-term consequence, DISC1 knock-down in immune-challenged mice leads to poorer recognition memory at pre-juvenile age. Thus, besides PFC, hippocampal CA1 area has a critical role for the developmental miswiring and long-lasting cognitive impairment related to mental illness.Significance StatementDevelopmental miswiring within prefrontal-hippocampal networks has been proposed to account for cognitive impairment in mental disorders. Indeed, during development, long before the emergence of cognitive deficits, the functional coupling within these networks is reduced in mouse models of disease. However, the cellular mechanisms of dysfunction are largely unknown. Here we combine in vivo electrophysiology and optogenetics with behavioral assessment in immune-challenged mice with hippocampus-confined DISC1 knock-down and show that pyramidal neurons in CA1 area are critical for the developmental dysfunction of prefrontal-hippocampal communication and cognitive impairment.

scholarly journals Dementia Enhances Inhibitory Actions of General Anesthetics in Hippocampal Synaptic Transmission

2011 ◽  
Vol 2011 ◽  
pp. 1-5
Author(s):  
Masana Yamada ◽  
Rika Sasaki ◽  
Koki Hirota ◽  
Mitsuaki Yamazaki
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Gaba Release ◽  
Recurrent Inhibition ◽  
General Anesthetics ◽  
Presynaptic Terminals ◽  
Loss Of Righting Reflex ◽  
Healthy Control

In order to investigate whether dementia modifies the anesthetic actions in the central nervous systems, we have studied effects of general anesthetics on the hippocampal synaptic transmission using the dementia model mice. Preliminary in vivo experiments revealed that time of loss of righting reflex following sevoflurane inhalation was more shortened in dementia mice than in healthy control mice. Field population spikes of hippocampal CA1 pyramidal neurons were elicited in vitro using orthodromic stimulation of Schaffer collateral commissural fibers (test pulse). The recurrent inhibition was enhanced with the second stimulating electrode placed in alveus hippocampi (prepulse) to activate recurrent inhibition of CA1. The prepulses were applied as train stimuli to activate release and then deplete γ-amino-butyric acid (GABA) at presynaptic terminals of inhibitory interneurons. Sevoflurane and thiopental had greater actions on inhibitory synaptic transmission in dementia model mice than in control mice. The pre-pulse train protocol revealed that the anesthetic-induced GABA discharge was more enhanced in dementia mice than in control mice. Dementia enhances the actions of general anesthetics due to the increase in GABA release from presynaptic terminals.

scholarly journals Consequences of human Tau aggregation in the hippocampal formation of ageing mice in vivo

2021 ◽  
Author(s):  
Tim J Viney ◽  
Barbara Sarkany ◽  
A Tugrul Ozdemir ◽  
Katja Hartwich ◽  
Judith Schweimer ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Pyramidal Neurons ◽  
Hippocampal Formation ◽  
Pyramidal Cells ◽  
Reference Memory ◽  
Network Activity ◽  
Motor Impairments ◽  
Tau Aggregation ◽  
High Firing

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing pyramidal cells, with the remaining cells retaining their coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely-moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms implementing cortical neuronal coordination compensate for the widespread pTau aggregation, loss of high-firing cells and neurodegeneration.

scholarly journals Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Matthieu Raveau ◽  
Denis Polygalov ◽  
Roman Boehringer ◽  
Kenji Amano ◽  
Kazuhiro Yamakawa ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Pyramidal Neurons ◽  
Chromosome 21 ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Spatial Coding ◽  
Extra Copy ◽  
Hippocampal Ca1

Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the ‘over-suppression’ theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice.

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