scholarly journals Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex

2012 ◽  
Vol 107 (11) ◽  
pp. 3116-3134 ◽  
Author(s):  
Michael Avermann ◽  
Christian Tomm ◽  
Celine Mateo ◽  
Wulfram Gerstner ◽  
Carl C. H. Petersen
Keyword(s):  
Barrel Cortex ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Postsynaptic Potentials ◽  
Optogenetic Stimulation ◽  
Layer 2 ◽  
Fast Spiking ◽  
Whole Cell Recordings

Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo.

scholarly journals Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

2021 ◽  
Vol 17 ◽  
pp. 174480692199262
Author(s):  
Peng Liu ◽  
Xiao Zhang ◽  
Xiaolan He ◽  
Zhenhua Jiang ◽  
Qun Wang ◽  
...  
Keyword(s):  
Inhibitory Control ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Feed Forward ◽  
Postsynaptic Potentials ◽  
Transgenic Mouse Line ◽  
C Fibers ◽  
Sensory Transmission ◽  
Whole Cell Recordings

Background Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. Methods We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. Results We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). Conclusion These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.

Auditory Thalamocortical Transmission Is Reliable and Temporally Precise

2005 ◽  
Vol 94 (3) ◽  
pp. 2019-2030 ◽  
Author(s):  
Heather J. Rose ◽  
Raju Metherate
Keyword(s):  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Latency Variability ◽  
Medial Geniculate ◽  
Low Jitter ◽  
Fast Spiking ◽  
Whole Cell Recordings ◽  
Minimal Stimulation ◽  
Juvenile Mouse

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. “Minimal” stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was ∼1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2–300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates ≥40 Hz, EPSPs also summed to activate N-methyl-d-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.

Development of Intrinsic Properties and Excitability of Layer 2/3 Pyramidal Neurons During a Critical Period for Sensory Maps in Rat Barrel Cortex

2004 ◽  
Vol 92 (1) ◽  
pp. 144-156 ◽  
Author(s):  
Miguel Maravall ◽  
Edward A. Stern ◽  
Karel Svoboda
Keyword(s):  
Critical Period ◽  
Pyramidal Neurons ◽  
Barrel Cortex ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Sensory Maps ◽  
Layer 2 ◽  
Whole Cell Recordings ◽  
Passive Membrane Properties

The development of layer 2/3 sensory maps in rat barrel cortex (BC) is experience dependent with a critical period around postnatal days (PND) 10–14. The role of intrinsic response properties of neurons in this plasticity has not been investigated. Here we characterize the development of BC layer 2/3 intrinsic responses to identify possible sites of plasticity. Whole cell recordings were performed on pyramidal cells in acute BC slices from control and deprived rats, over ages spanning the critical period (PND 12, 14, and 17). Vibrissa trimming began at PND 9. Spiking behavior changed from phasic (more spike frequency adaptation) to regular (less adaptation) with age, such that the number of action potentials per stimulus increased. Changes in spiking properties were related to the strength of a slow Ca2+-dependent afterhyperpolarization. Maturation of the spiking properties of layer 2/3 pyramidal neurons coincided with the close of the critical period and was delayed by deprivation. Other measures of excitability, including I-f curves and passive membrane properties, were affected by development but unaffected by whisker deprivation.

scholarly journals Neocortical inhibitory interneuron subtypes display distinct responses to synchrony and rate of inputs

2019 ◽  
Author(s):  
Matthew M. Tran ◽  
Luke Y. Prince ◽  
Dorian Gray ◽  
Lydia Saad ◽  
Helen Chasiotis ◽  
...  
Keyword(s):  
Mutual Information ◽  
Barrel Cortex ◽  
Inhibitory Interneuron ◽  
Optical Stimulation ◽  
Layer 2 ◽  
Fast Spiking ◽  
Cortical Microcircuit ◽  
Negative Controls ◽  
Mouse Lines ◽  
Stimulation Of

AbstractPopulations of neurons in the neocortex can carry information with both the synchrony and the rate of their spikes. However, it is unknown whether distinct subtypes of neurons in the cortical microcircuit are more sensitive to information carried by synchrony versus rate. Here, we address this question using patterned optical stimulation in slices of barrel cortex from transgenic mouse lines labelling distinct interneuron populations: fast-spiking parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons. We use optical stimulation of channelrhodopsin-2 (ChR2) expressing excitatory neurons in layer 2/3 in order to encode a random 1-bit signal in either the synchrony or rate of activity in presynaptic cells. We then examine the mutual information between this 1-bit signal and the voltage and spiking responses in PV+ and SST+ interneurons. Generally, we find that both interneuron types carry more information than GFP negative (GFP-) control cells. More specifically, we find that for a synchrony encoding, PV+ interneurons carry more information in the first 5 milliseconds, while both interneuron subtypes carry more information than negative controls in their later response. We also find that for a rate encoding, SST+ interneurons carry more information than either PV+ or negative controls after several milliseconds. These data demonstrate that inhibitory interneuron subtypes in the neocortex have distinct responses to information carried by synchrony versus rates of spiking.

Lack of Depolarization-Induced Suppression of Inhibition (DSI) in Layer 2/3 Interneurons That Receive Cannabinoid-Sensitive Inhibitory Inputs

2007 ◽  
Vol 98 (5) ◽  
pp. 2517-2524 ◽  
Author(s):  
Fouad Lemtiri-Chlieh ◽  
Eric S. Levine
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Cannabinoid Receptor ◽  
Brain Slices ◽  
Gaba Release ◽  
Synaptic Activity ◽  
Layer 2 ◽  
Fast Spiking ◽  
Whole Cell Recordings

In layer 2/3 of neocortex, brief trains of action potentials in pyramidal neurons (PNs) induce the mobilization of endogenous cannabinoids (eCBs), resulting in a depression of GABA release from the terminals of inhibitory interneurons (INs). This depolarization-induced suppression of inhibition (DSI) is mediated by activation of the type 1 cannabinoid receptor (CB1) on presynaptic terminals of a subset of INs. However, it is not clear whether CB1 receptors are also expressed at synapses between INs, and whether INs can release eCBs in response to depolarization. In the present studies, brain slices containing somatosensory cortex were prepared from 14- to 21-day-old CD-1 mice. Whole cell recordings were obtained from layer 2/3 PNs and from INs classified as regular spiking nonpyramidal, irregular spiking, or fast spiking. For all three classes of INs, the cannabinoid agonist WIN55,212-2 suppressed inhibitory synaptic activity, similar to the effect seen in PNs. In addition, trains of action potentials in PNs resulted in significant DSI. In INs, however, DSI was not seen in any cell type, even with prolonged high-frequency spike trains that produced calcium increases comparable to that seen with DSI induction in PNs. In addition, blocking eCB reuptake with AM404, which enhanced DSI in PNs, failed to unmask any DSI in INs. Thus the lack of DSI in INs does not appear to be due to an insufficient increase in intracellular calcium or enhanced reuptake. These results suggest that layer 2/3 INs receive CB1-expressing inhibitory inputs, but that eCBs are not released by these INs.

scholarly journals Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation

2020 ◽  
Author(s):  
Elena Tantillo ◽  
Eleonora Vannini ◽  
Chiara Cerri ◽  
Cristina Spalletti ◽  
Antonella Colistra ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Pyramidal Neurons ◽  
Visual Stimulation ◽  
Afferent Input ◽  
Gabaergic Neurons ◽  
Optogenetic Stimulation ◽  
Glioma Cell Proliferation ◽  
Fast Spiking ◽  
Stimulation Of

AbstractRecent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different subsets of cortical neurons, such as GABAergic interneurons, remains unexplored. Here, we directly compared the effects of optogenetic stimulation of pyramidal cells vs. fast-spiking, GABAergic neurons. In mice inoculated with GL261 cells into the motor cortex, we show that optogenetic stimulation of pyramidal neurons enhances glioma cell proliferation. In contrast, optogenetic stimulation of fast-spiking, parvalbumin-positive interneurons reduces proliferation as measured by BrdU incorporation and Ki67 immunolabelling. Since both principal cells and fast-spiking interneurons are directly activated by sensory afferent input, we next placed tumors in the occipital cortex to test the impact of visual stimulation/deprivation. We report that total lack of visual input via dark rearing enhances the density of proliferating glioma cells, while daily visual stimulation by gratings of different spatial frequencies and contrast reduces tumor growth. The effects of sensory input are region-specific, as visual deprivation has no significant effect on tumor proliferation in mice with gliomas in the motor cortex. We also report that sensory stimulation combined with temozolomide administration delays the loss of visual responses in peritumoral neurons. Altogether, these data demonstrate complex effects of different neuronal subtypes in the control of glioma proliferation.HighlightsActivity of GABAergic neurons reduces glioma cell proliferationLevels of sensory afferent input regulate tumor proliferationEffects of sensory input are region-specific

scholarly journals Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

2019 ◽  
Author(s):  
Kai Yu ◽  
Xiaodan Niu ◽  
Esther Krook-Magnuson ◽  
Bin He
Keyword(s):  
Focused Ultrasound ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Fast Spiking ◽  
First Time ◽  
Transcranial Focused Ultrasound ◽  
Specific Neuron ◽  
Ultrasound Pulse

ABSTRACTTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains. Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.

scholarly journals Dendritic inhibition differentially regulates excitability of dentate gyrus parvalbumin-expressing interneurons and granule cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Claudio Elgueta ◽  
Marlene Bartos
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Network Activity ◽  
Global Network ◽  
Perforant Path ◽  
Input Output ◽  
Inhibitory Effects ◽  
Cell Modeling ◽  
Fast Spiking ◽  
Whole Cell Recordings

AbstractFast-spiking parvalbumin-expressing interneurons (PVIs) and granule cells (GCs) of the dentate gyrus receive layer-specific dendritic inhibition. Its impact on PVI and GC excitability is, however, unknown. By applying whole-cell recordings, GABA uncaging and single-cell-modeling, we show that proximal dendritic inhibition in PVIs is less efficient in lowering perforant path-mediated subthreshold depolarization than distal inhibition but both are highly efficient in silencing PVIs. These inhibitory effects can be explained by proximal shunting and distal strong hyperpolarizing inhibition. In contrast, GC proximal but not distal inhibition is the primary regulator of their excitability and recruitment. In GCs inhibition is hyperpolarizing along the entire somato-dendritic axis with similar strength. Thus, dendritic inhibition differentially controls input-output transformations in PVIs and GCs. Dendritic inhibition in PVIs is suited to balance PVI discharges in dependence on global network activity thereby providing strong and tuned perisomatic inhibition that contributes to the sparse representation of information in GC assemblies.

scholarly journals Cell-type specific neuromodulation of excitatory and inhibitory neurons via muscarinic acetylcholine receptors in layer 4 of rat barrel cortex

2021 ◽  
Author(s):  
Guanxiao Qi ◽  
Dirk Feldmeyer
Keyword(s):  
Barrel Cortex ◽  
Muscarinic Acetylcholine Receptors ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Specific Expression ◽  
Low Concentrations ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spiking ◽  
Ach Receptors

The neuromodulator acetylcholine (ACh) plays an important role in arousal, attention, vigilance, learning and memory. ACh is released during different behavioural states and affects the brain microcircuit by regulating neuronal and synaptic properties. Here, we investigated how a low concentration of ACh (30 μM) affects the intrinsic properties of electrophysiologically and morphologically identified excitatory and inhibitory neurons in layer 4 (L4) of rat barrel cortex. ACh altered the membrane potential of L4 neurons in a heterogeneous manner. Nearly all L4 regular spiking (RS) neurons responded to bath-application of ACh with a M4 muscarinic ACh receptor-mediated hyperpolarisation. In contrast, in the majority of L4 fast spiking (FS) and non-fast spiking (nFS) interneurons 30 μM ACh induced a depolarisation while the remainder showed a hyperpolarisation or no response. The ACh-induced depolarisation of L4 FS interneurons was much weaker than that in L4 nFS interneurons. There was no clear difference in the response to ACh for three morphological subtypes of L4 FS interneurons. However, in four morpho-electrophysiological subtypes of L4 nFS interneurons, VIP+-like interneurons showed the strongest ACh-induced depolarisation; occasionally, even action potential (AP) firing was elicited. The ACh-induced depolarisation in L4 FS interneurons was exclusively mediated by M1 muscarinic ACh receptors; in L4 nFS interneurons it was mainly mediated by M1 and/or M3/5 muscarinic ACh receptors. In a subset of L4 nFS interneurons, a co-operative activation of nicotinic ACh receptors was also observed. The present study demonstrates that low-concentrations of ACh affect the different L4 neurons types in a cell-type specific way. These effects result from a specific expression of different muscarinic and/or nicotinic ACh receptors on the somatodendritic compartments of L4 neurons. This suggests that even at low concentrations ACh may tune the excitability of L4 excitatory and inhibitory neurons and their synaptic microcircuits differentially depending on the behavioural state during which ACh is released.

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