scholarly journals Temporal gating of synaptic competition in the lateral amygdala by cannabinoid receptor modulation of the thalamic input

2019 ◽  
Author(s):  
Ana Drumond ◽  
Natália Madeira ◽  
Rosalina Fonseca
Keyword(s):  
Synaptic Plasticity ◽  
Cannabinoid Receptor ◽  
Critical Role ◽  
Action Potential Firing ◽  
Lateral Amygdala ◽  
Cooperation And Competition ◽  
Thalamic Stimulation ◽  
Receptor Modulation ◽  
Gating Mechanism ◽  
Potential Firing

ABSTRACTThe acquisition of fear memories involves plasticity of the thalamic and cortical pathways to the lateral amygdala (LA). The maintenance of synaptic plasticity requires the interplay between input-specific synaptic tags and the allocation of plasticity-related proteins (PRPs). Based on this interplay, weakly activated synapses can express long-lasting synaptic plasticity by cooperation with strongly activated ones. Increasing the number of activated synapses can shift cooperation to competition. Synaptic cooperation and competition can determine whether two events, separated in time, are linked or selected. The rules that determine whether synapses cooperate or compete are unknown. We found that synaptic cooperation and competition, in the LA, are determined by the temporal sequence of cortical and thalamic stimulation and that the strength of the synaptic tag is modulated by the endocannabinoid signalling. This modulation is particularly effective in thalamic synapses, suggesting a critical role of endocannabinoids in restricting thalamic plasticity. Also, we found that PRPs availability is modulated by the action-potential firing of neurons, shifting competition to cooperation. Our data present the first evidence that pre-synaptic modulation of synaptic activation, by the cannabinoid signalling, function as a temporal gating mechanism limiting synaptic cooperation and competition.

scholarly journals Temporal Gating of Synaptic Competition in the Amygdala by Cannabinoid Receptor Activation

2020 ◽  
Vol 30 (7) ◽  
pp. 4064-4075 ◽  
Author(s):  
Natália Madeira ◽  
Ana Drumond ◽  
Rosalina Fonseca
Keyword(s):  
Synaptic Plasticity ◽  
Cannabinoid Receptor ◽  
Critical Role ◽  
Receptor Activation ◽  
Synaptic Proteins ◽  
Synaptic Competition ◽  
Cooperation And Competition ◽  
Thalamic Stimulation ◽  
Gating Mechanism ◽  
Related Proteins

Abstract The acquisition of fear memories involves plasticity of the thalamic and cortical pathways to the lateral amygdala (LA). In turn, the maintenance of synaptic plasticity requires the interplay between input-specific synaptic tags and the allocation of plasticity-related proteins. Based on this interplay, weakly activated synapses can express long-lasting forms of synaptic plasticity by cooperating with strongly activated synapses. Increasing the number of activated synapses can shift cooperation to competition. Synaptic cooperation and competition can determine whether two events, separated in time, are associated or whether a particular event is selected for storage. The rules that determine whether synapses cooperate or compete are unknown. We found that synaptic cooperation and competition, in the LA, are determined by the temporal sequence of cortical and thalamic stimulation and that the strength of the synaptic tag is modulated by the endocannabinoid signaling. This modulation is particularly effective in thalamic synapses, supporting a critical role of endocannabinoids in restricting thalamic plasticity. Also, we found that the availability of synaptic proteins is activity-dependent, shifting competition to cooperation. Our data present the first evidence that presynaptic modulation of synaptic activation, by the cannabinoid signaling, functions as a temporal gating mechanism limiting synaptic cooperation and competition.

scholarly journals The GluN2A subunit of the NMDA receptor modulates the rate of functional maturation in parvalbumin-positive interneurons

2021 ◽  
Author(s):  
Chad R Camp ◽  
Lindsey Shapiro ◽  
Anna Vlachos ◽  
Riley E Perszyk ◽  
Nima Shariatzadeh ◽  
...  
Keyword(s):  
Action Potential ◽  
Expression Pattern ◽  
Knockout Mice ◽  
Time Course ◽  
Neuronal Development ◽  
Critical Role ◽  
Gabaergic Interneuron ◽  
Wild Type ◽  
Action Potential Firing ◽  
Potential Firing

N-methyl-D-aspartate receptors (NMDARs) are excitatory glutamate-gated ion channels that are expressed throughout the central nervous system. NMDARs mediate calcium entry into cells, and are involved in a host of neurological functions, including neuronal development and maturation. The GluN2A subunit, encoded by the GRIN2A gene, has a slightly delayed expression pattern, with low transcript levels during embryonic development that peak in the early neonatal period. Given its unique expression pattern and ability to speed up the synaptic time course after incorporation into the postsynaptic density compared to other GluN2 subunits, the GluN2A subunit is well positioned to participate in synaptic maturation and circuit refinement. By using Grin2a knockout mice, we show that the loss of GluN2A signaling impacts parvalbumin-positive GABAergic interneuron development in the hippocampal CA1 subfield. Specifically, Grin2a knockout mice have 33% more parvalbumin-positive cells in CA1 compared to wild type controls, with no impact on cholecystokinin-positive cell density. By using immunohistochemical colocalization staining and electrophysiological recordings, we demonstrate that these excess parvalbumin cells do eventually incorporate into the hippocampal network and participate in phasic inhibition, although their presynaptic release probability may be dampened. Moreover, we show that although the morphology of Grin2a knockout parvalbumin-positive cells is unaffected, key measures of intrinsic excitability and action-potential firing properties show age-dependent alterations. Preadolescent (P20-25) parvalbumin-positive cells have an increased input resistance, longer membrane time constant, longer action-potential half-width, a lower current threshold for depolarization-induced block of action-potential firing, and a decrease in peak action-potential firing rate. Each of these electrophysiological measures becomes corrected in adulthood, reaching wild type levels, suggesting a delay of electrophysiological maturation. The circuit and behavioral implications of delayed parvalbumin-positive interneuron maturation are not known; however, we find that neonatal Grin2a knockout mice are more susceptible to lipopolysaccharide and febrile-induced seizures, consistent with a critical role for early GluN2A signaling in neuronal development and maintenance of excitatory-inhibitory balance. These results could provide insights into how loss-of-function GRIN2A human variants can generate an epileptic phenotype.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

scholarly journals The thalamic low-threshold Ca 2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

2011 ◽  
Vol 369 (1952) ◽  
pp. 3820-3839 ◽  
Author(s):  
Vincenzo Crunelli ◽  
Adam C. Errington ◽  
Stuart W. Hughes ◽  
Tibor I. Tóth
Keyword(s):  
Action Potential ◽  
Slow Oscillation ◽  
Global Dynamics ◽  
Action Potential Firing ◽  
Local And Global Dynamics ◽  
Up States ◽  
Potential Firing ◽  
Low Threshold

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca 2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca 2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.

BICUCULLINE/BACLOFEN-INSENSITIVE GABA RESPONSE IN CRUSTACEAN NEURONES IN CULTURE

1994 ◽  
Vol 191 (1) ◽  
pp. 167-193
Author(s):  
C Jackel ◽  
W Krenz ◽  
F Nagy
Keyword(s):  
Reversal Potential ◽  
Membrane Conductance ◽  
Gamma Aminobutyric Acid ◽  
Action Potential Firing ◽  
Patch Clamp Technique ◽  
Conformationally Restricted ◽  
Whole Cell Patch Clamp ◽  
Gabac Receptor ◽  
Potential Firing ◽  
Sr 95531

Neurones were dissociated from thoracic ganglia of embryonic and adult lobsters and kept in primary culture. When gamma-aminobutyric acid (GABA) was applied by pressure ejection, depolarizing or hyperpolarizing responses were produced, depending on the membrane potential. They were accompanied by an increase in membrane conductance. When they were present, action potential firing was inhibited. The pharmacological profile and ionic mechanism of GABA-evoked current were investigated under voltage-clamp with the whole-cell patch-clamp technique. The reversal potential of GABA-evoked current depended on the intracellular and extracellular Cl- concentration but not on extracellular Na+ and K+. Blockade of Ca2+ channels by Mn2+ was also without effect. The GABA-evoked current was mimicked by application of the GABAA agonists muscimol and isoguvacine with an order of potency muscimol&gt;GABA&gt;isoguvacine. cis-4-aminocrotonic acid (CACA), a folded and conformationally restricted GABA analogue, supposed to be diagnostic for the vertebrate GABAC receptor, also induced a bicuculline-resistant chloride current, although with a potency about 10 times lower than that of GABA. The GABA-evoked current was largely blocked by picrotoxin, but was insensitive to the GABAA antagonists bicuculline, bicuculline methiodide and SR 95531 at concentrations of up to 100 &micro;mol l-1. Diazepam and phenobarbital did not exert modulatory effects. The GABAB antagonist phaclophen did not affect the GABA-induced current, while the GABAB agonists baclophen and 3-aminopropylphosphonic acid (3-APA) never evoked any response. Our results suggest that lobster thoracic neurones in culture express a chloride-conducting GABA-receptor channel which conforms to neither the GABAA nor the GABAB types of vertebrates but shows a pharmacology close to that of the novel GABAC receptor described in the vertebrate retina.

scholarly journals pigkMutation underliesmachobehavior and affects Rohon-Beard cell excitability

2015 ◽  
Vol 114 (2) ◽  
pp. 1146-1157 ◽  
Author(s):  
V. Carmean ◽  
M. A. Yonkers ◽  
M. B. Tellez ◽  
J. R. Willer ◽  
G. B. Willer ◽  
...  
Keyword(s):  
Action Potential ◽  
Sensory Neurons ◽  
Sodium Current ◽  
Genetic Defect ◽  
Sensory Cells ◽  
Loss Of Function ◽  
Wild Type ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Touch Response

The study of touch-evoked behavior allows investigation of both the cells and circuits that generate a response to tactile stimulation. We investigate a touch-insensitive zebrafish mutant, macho (maco), previously shown to have reduced sodium current amplitude and lack of action potential firing in sensory neurons. In the genomes of mutant but not wild-type embryos, we identify a mutation in the pigk gene. The encoded protein, PigK, functions in attachment of glycophosphatidylinositol anchors to precursor proteins. In wild-type embryos, pigk mRNA is present at times when mutant embryos display behavioral phenotypes. Consistent with the predicted loss of function induced by the mutation, knock-down of PigK phenocopies maco touch insensitivity and leads to reduced sodium current (INa) amplitudes in sensory neurons. We further test whether the genetic defect in pigk underlies the maco phenotype by overexpressing wild-type pigk in mutant embryos. We find that ubiquitous expression of wild-type pigk rescues the touch response in maco mutants. In addition, for maco mutants, expression of wild-type pigk restricted to sensory neurons rescues sodium current amplitudes and action potential firing in sensory neurons. However, expression of wild-type pigk limited to sensory cells of mutant embryos does not allow rescue of the behavioral touch response. Our results demonstrate an essential role for pigk in generation of the touch response beyond that required for maintenance of proper INa density and action potential firing in sensory neurons.

Sign in / Sign up

Export Citation Format

Share Document