scholarly journals Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies

2018 ◽  
Author(s):  
Jonathan Cornford ◽  
Marion S Mercier ◽  
Marco Leite ◽  
Vincent Magloire ◽  
Michael Häusser ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Feedback Inhibition ◽  
Gaba Release ◽  
Gamma Oscillations ◽  
Network Function ◽  
Pv Cell ◽  
Action Potential Initiation ◽  
Spiking Networks ◽  
Feedback Connections

AbstractParvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment, action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.

scholarly journals Dendritic NMDA receptors in parvalbumin neurons enable strong and stable neuronal assemblies

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jonathan H Cornford ◽  
Marion S Mercier ◽  
Marco Leite ◽  
Vincent Magloire ◽  
Michael Häusser ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Feedback Inhibition ◽  
Gaba Release ◽  
Gamma Oscillations ◽  
Network Function ◽  
Pv Cell ◽  
Action Potential Initiation ◽  
Spiking Networks ◽  
Feedback Connections

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment and action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells, is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their potential importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.

scholarly journals Glycine transporter 1 modulates GABA release from amacrine cells by controlling occupancy of coagonist binding site of NMDA receptors

2013 ◽  
Vol 110 (6) ◽  
pp. 1393-1403 ◽  
Author(s):  
Eva Rozsa ◽  
Jozsef Vigh
Keyword(s):  
Nmda Receptors ◽  
Binding Sites ◽  
Feedback Inhibition ◽  
Glycine Receptor ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Axon Terminals ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Nmdar Activation

The occupancy of coagonist binding sites of NMDA receptors (NMDARs) by glycine or d-serine has been thought to mediate NMDAR-dependent excitatory signaling, as simultaneous binding of glutamate and a coagonist is obligatory for NMDAR activation. Amacrine cells (ACs) mediating GABAergic feedback inhibition of mixed bipolar cells (Mbs) in the goldfish retina have been shown to express NMDARs. Here we studied whether NMDAR-mediated GABAergic inhibitory currents ( IGABA) recorded from the axon terminals of Mbs are influenced by experimental manipulations altering retinal glycine and d-serine levels. Feedback IGABA in Mb axon terminals was triggered by focal NMDA application or by synaptically released glutamate from depolarized Mb terminals. In both cases, blocking the coagonist binding sites of NMDARs eliminated the NMDAR-dependent IGABA, demonstrating that coagonist binding is critical in mediating NMDAR activity-triggered GABA release. Glycine transporter 1 (GLYT1) inhibition increased IGABA, indicating that coagonist binding sites of NMDARs on ACs providing GABAergic feedback inhibition to Mbs were not saturated. Focal glycine application, in the presence of the ionotropic glycine receptor blocker strychnine, triggered a GLYT1-dependent current in ACs, suggesting that GLYT1 expressed by putative glycinergic ACs controls the saturation level of NMDARs' coagonist sites. External d-serine also increased NMDAR activation-triggered IGABA in Mbs, further substantiating that the coagonist sites were unsaturated. Together, our findings demonstrate that coagonist modulation of glutamatergic input to GABAergic ACs via NMDARs is strongly reflected in the AC neuronal output (i.e., transmitter release) and thus is critical in GABAergic signal transfer function in the inner retina.

Parvalbumin-Deficiency Facilitates Repetitive IPSCs and Gamma Oscillations in the Hippocampus

2003 ◽  
Vol 89 (3) ◽  
pp. 1414-1422 ◽  
Author(s):  
Martin Vreugdenhil ◽  
John G. R. Jefferys ◽  
Marco R. Celio ◽  
Beat Schwaller
Keyword(s):  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Field Potential ◽  
Gaba Release ◽  
Gamma Oscillations ◽  
Dominant Frequency ◽  
Experimental Conditions ◽  
Gamma Power ◽  
Gamma Frequencies ◽  
Higher Cognitive Functions

In the hippocampus, the calcium-binding protein parvalbumin (PV) is expressed in interneurons that innervate perisomatic regions. PV in GABAergic synaptic terminals was proposed to limit repetitive GABA release by buffering of “residual calcium.” We assessed the role of presynaptic PV in Ca2+-dependent GABA release in the hippocampus of PV-deficient (PV−/−) mice and wild-type (PV+/+) littermates. Pharmacologically isolated inhibitory postsynaptic currents (IPSCs) were evoked by low-intensity stimulation of the stratum pyramidale and recorded from voltage-clamped CA1 pyramidal neurons. The amplitude and decay time constant of single IPSCs were similar for both genotypes. Under our experimental conditions of reduced release probability and minimal presynaptic suppression, paired-pulse facilitation of IPSCs occurred at intervals from 2 to 50 ms, irrespective of the presence of PV. The facilitation of IPSCs induced by trains of 10 stimuli at frequencies >20 Hz was enhanced in cells from PV−/− mice, the largest difference between PV−/− and PV+/+ animals (220%) being observed at 33 Hz. The effect of IPSC facilitation at sustained gamma frequencies was assessed on kainate-induced rhythmic IPSC-paced neuronal oscillations at gamma frequencies, recorded with dual field potential recordings in area CA3. The maximum power of the oscillation was 138 μV2 at 36 Hz in slices from PV+/+ mice and was trebled in slices from PV−/− mice. PV deficiency caused a similar increase in gamma power under conditions used to study IPSC facilitation and can be explained by an increased facilitation of GABA release at sustained high frequencies. The dominant frequency and coherence were not affected by PV deficiency. These observations suggest that PV deficiency, due to an increased short-term facilitation of GABA release, enhances inhibition by high-frequency burst-firing PV-expressing interneurons and may affect the higher cognitive functions associated with gamma oscillations.

Physiological Properties of Late Inspiratory Neurons and Their Possible Involvement in Inspiratory Off-Switching in Cats

2002 ◽  
Vol 87 (2) ◽  
pp. 1057-1067 ◽  
Author(s):  
Akira Haji ◽  
Mari Okazaki ◽  
Hiromi Yamazaki ◽  
Ryuji Takeda
Keyword(s):  
Nmda Receptors ◽  
Gaba Release ◽  
Membrane Depolarization ◽  
Inhibitory Neurons ◽  
Acid Decarboxylase ◽  
Postsynaptic Potentials ◽  
Inspiratory Neurons ◽  
Small Constant ◽  
Physiological Properties ◽  
Decerebrate Cats

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-d-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.

GABA release triggered by the activation of neuron-like non-NMDA receptors in cultured type 2 astrocytes is carrier-mediated

Glia ◽  
1991 ◽  
Vol 4 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Vittorio Gallo ◽  
Mario Patrizio ◽  
Giulio Levi
Keyword(s):  
Nmda Receptors ◽  
Gaba Release

Cholinergic modulation of synaptic inhibition in the guinea pig hippocampus in vitro: excitation of GABAergic interneurons and inhibition of GABA-release

1993 ◽  
Vol 69 (2) ◽  
pp. 626-629 ◽  
Author(s):  
J. C. Behrends ◽  
G. ten Bruggencate
Keyword(s):  
Guinea Pig ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Gaba Release ◽  
Cholinergic Receptor ◽  
Receptor Activation ◽  
Release Mechanism ◽  
Gabaergic Interneurons ◽  
Gamma Aminobutyric Acid

1. The effect of cholinergic receptor activation on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission was investigated in voltage-clamped CA1 pyramidal neurons (HPNs) in the guinea pig hippocampal slice preparation. 2. The cholinergic agonist carbachol (1-10 microM) induced a prominent and sustained increase in the frequency and amplitudes of spontaneous inhibitory postsynaptic currents (IPSCs) in Cl(-)-loaded HPNs. The potentiation of spontaneous IPSCs was not dependent on excitatory synaptic transmission but was blocked by atropine (1 microM). 3. Monosynaptically evoked IPSCs were reversibly depressed by carbachol (10 microM). 4. The frequency of miniature IPSCs recorded in the presence of tetrodotoxin (0.6 or 1.2 microM) was reduced by carbachol (10 or 20 microM) in an atropine-sensitive manner. 5. We conclude that, while cholinergic receptor activation directly excites hippocampal GABAergic interneurons, it has, in addition, a suppressant effect on the synaptic release mechanism at GABAergic terminals. This dual modulatory pattern could explain the suppression of evoked IPSCs despite enhanced spontaneous transmission.

scholarly journals Integration, coincidence detection and resonance in networks of spiking neurons expressing Gamma oscillations and asynchronous states

2021 ◽  
Vol 17 (9) ◽  
pp. e1009416
Author(s):  
Eduarda Susin ◽  
Alain Destexhe
Keyword(s):  
Cerebral Cortex ◽  
Pyramidal Neurons ◽  
Network Models ◽  
Cell Types ◽  
Gamma Oscillations ◽  
Coincidence Detection ◽  
Biophysical Models ◽  
Firing Mode ◽  
Different Cell Types ◽  
External Stimuli

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how Gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of Gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where Gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate Gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which Gamma is generated by interneuron networks (ING) and third, a mechanism which relies on Gamma oscillations generated by pacemaker chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting Gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.

scholarly journals Learning excitatory-inhibitory neuronal assemblies in recurrent networks

2020 ◽  
Author(s):  
Owen Mackwood ◽  
Laura B. Naumann ◽  
Henning Sprekeler
Keyword(s):  
Pyramidal Neurons ◽  
Feedback Inhibition ◽  
Recent Experimental Data ◽  
Similar Stimulus ◽  
Inhibitory Circuits ◽  
Circuit Structure ◽  
Specific Feedback ◽  
Stimulus Features ◽  
Synaptic Circuitry ◽  
Activity Dependent

AbstractIn sensory circuits with poor feature topography, stimulus-specific feedback inhibition necessitates carefully tuned synaptic circuitry. Recent experimental data from mouse primary visual cortex (V1) show that synapses between pyramidal neurons and parvalbumin-expressing (PV) inhibitory interneurons tend to be stronger for neurons that respond to similar stimulus features. The mechanism that underlies the formation of such excitatory-inhibitory (E/I) assemblies is unresolved. Here, we show that activity-dependent synaptic plasticity on input and output synapses of PV interneurons generates a circuit structure that is consistent with mouse V1. Using a computational model, we show that both forms of plasticity must act synergistically to form the observed E/I assemblies. Once established, these assemblies produce a stimulus-specific competition between pyramidal neurons. Our model suggests that activity-dependent plasticity can enable inhibitory circuits to actively shape cortical computations.

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