Cholinergic modulation of dopamine release drives effortful behaviour - Nature In the nucleus accumbens, acetylcholine boosts dopamine release to promote effortful behaviour.

#Cholinergic modulation of #dopamine release drives effortful #behaviour
doi.org/10.1038/s415...

U01.05.012 Acetylcholine receptors Match each receptor type with its corresponding physiological function. Carefully drag the receptor name (e.g., Nn, Nm, M1, M2, M3, M4, M5) into the correct box describing its primary action. Focus on understanding which receptors are nicotinic (autonomic and neuromuscular) and which are muscarinic (parasympathetic targets). This exercise helps reinforce your knowledge of cholinergic receptor physiology — an essential topic for USMLE Step 1 and pharmacology exams.

Acetylcholine receptors include nicotinic and muscarinic types controlling muscle and autonomic functions. #AcetylcholineReceptors #Nicotinic #Muscarinic #Cholinergic #Neuropharmacology #Pharmacology #AutonomicNervousSystem #USMLE #MedicalEducation

Short axon cells of the olfactory bulb dynamically filter olfactory sensory input during attention and after learning. As mice learn to discriminate odors (left), providing a cue before presenting odors (top) improves performance by recruiting cholinergic signaling from the basal forebrain (ACh, blue) to inhibit short axon cells (SAC, magenta) which, in turn, disinhibits olfactory sensory neuron (OSN, green and orange) axon terminals in olfactory bulb glomeruli (dashed circles), and increases their signaling onto mitral and tufted cells (MTCs, gray). After learning (right), SACs remodel to make stronger contacts with reward-associated OSNs (top) and cholinergic signaling is disengaged during the cued period before odor presentations. Cholinergic signaling, however, is strongly recruited during presentations of the reward-associated odor (bottom), allowing disinhibition of reward-linked odor signaling from OSNs to MTCs.

This Primer explores two @plosbiology.org studies that reveal how short axon cells in the #OlfactoryBulb integrate #cholinergic input from the basal #forebrain to dynamically regulate #olfactory input 🧪Papers: plos.io/4pvost3 plos.io/3VnO1hT Primer: plos.io/3Ivzcqy

Short axon cells of the olfactory bulb dynamically filter olfactory sensory input during attention and after learning. As mice learn to discriminate odors (left), providing a cue before presenting odors (top) improves performance by recruiting cholinergic signaling from the basal forebrain (ACh, blue) to inhibit short axon cells (SAC, magenta) which, in turn, disinhibits olfactory sensory neuron (OSN, green and orange) axon terminals in olfactory bulb glomeruli (dashed circles), and increases their signaling onto mitral and tufted cells (MTCs, gray). After learning (right), SACs remodel to make stronger contacts with reward-associated OSNs (top) and cholinergic signaling is disengaged during the cued period before odor presentations. Cholinergic signaling, however, is strongly recruited during presentations of the reward-associated odor (bottom), allowing disinhibition of reward-linked odor signaling from OSNs to MTCs.

This Primer explores two @plosbiology.org studies that reveal how short axon cells in the #OlfactoryBulb integrate #cholinergic input from the basal #forebrain to dynamically regulate #olfactory input 🧪Papers: plos.io/4pvost3 plos.io/3VnO1hT Primer: plos.io/3Ivzcqy

Short axon cells of the olfactory bulb dynamically filter olfactory sensory input during attention and after learning. As mice learn to discriminate odors (left), providing a cue before presenting odors (top) improves performance by recruiting cholinergic signaling from the basal forebrain (ACh, blue) to inhibit short axon cells (SAC, magenta) which, in turn, disinhibits olfactory sensory neuron (OSN, green and orange) axon terminals in olfactory bulb glomeruli (dashed circles), and increases their signaling onto mitral and tufted cells (MTCs, gray). After learning (right), SACs remodel to make stronger contacts with reward-associated OSNs (top) and cholinergic signaling is disengaged during the cued period before odor presentations. Cholinergic signaling, however, is strongly recruited during presentations of the reward-associated odor (bottom), allowing disinhibition of reward-linked odor signaling from OSNs to MTCs.

This Primer explores two @plosbiology.org studies that reveal how short axon cells in the #OlfactoryBulb integrate #cholinergic input from the basal #forebrain to dynamically regulate #olfactory input 🧪Papers: plos.io/4pvost3 plos.io/3VnO1hT Primer: plos.io/3Ivzcqy

Modeling plasticity dependent selective attention. Schematic of the glomerular network model incorporating leaky-integrate-and-fire (LIF) neurons to simulate odor-driven activity and cholinergic modulation in the olfactory bulb. (i) Diagram showing selective activation of a subset of excitatory olfactory sensory neurons (OSNs, circles) by conditioned stimuli (CS+ or CS−). OSNs form reciprocal connections with inhibitory short axon cells (SACs, small circles with connections). CS+ trials (blue) selectively activate a specific OSN-SAC ensemble, while CS− trials (brown) activate a different subset. Network wiring enables targeted modulation of specific glomeruli based on stimulus identity. (ii) Valence-dependent synaptic changes within the OSN-SAC microcircuit. Differential cholinergic input (blue arrow for CS+, brown arrow for CS−) modulates SAC inhibition, shaping OSN-SAC connectivity via a Hebbian learning rule. Increased inhibition of SACs during CS+ trials promotes disinhibition of OSNs, enhancing their activity, while reduced inhibition during CS− trials maintains higher SAC-mediated suppression, thereby reducing bottom–up activation of SACs. (iii) Global cholinergic input simulating attention exerts uniform inhibition onto SACs across glomeruli. The functional impact is shaped by differential connectivity: SACs which have stronger inhibitory connections to OSNs, are more strongly suppressed by the same cholinergic signal, effectively biasing glomerular responses during attentive states.

Animals can use cues to initiate task preparation and amplify relevant #sensory input, but how? This study describes a circuit whereby an attentional cue triggers #cholinergic #forebrain activity, enhancing #olfactory responses (deactivated upon task-proficiency) @plosbiology.org 🧪 plos.io/3VnO1hT

Modeling plasticity dependent selective attention. Schematic of the glomerular network model incorporating leaky-integrate-and-fire (LIF) neurons to simulate odor-driven activity and cholinergic modulation in the olfactory bulb. (i) Diagram showing selective activation of a subset of excitatory olfactory sensory neurons (OSNs, circles) by conditioned stimuli (CS+ or CS−). OSNs form reciprocal connections with inhibitory short axon cells (SACs, small circles with connections). CS+ trials (blue) selectively activate a specific OSN-SAC ensemble, while CS− trials (brown) activate a different subset. Network wiring enables targeted modulation of specific glomeruli based on stimulus identity. (ii) Valence-dependent synaptic changes within the OSN-SAC microcircuit. Differential cholinergic input (blue arrow for CS+, brown arrow for CS−) modulates SAC inhibition, shaping OSN-SAC connectivity via a Hebbian learning rule. Increased inhibition of SACs during CS+ trials promotes disinhibition of OSNs, enhancing their activity, while reduced inhibition during CS− trials maintains higher SAC-mediated suppression, thereby reducing bottom–up activation of SACs. (iii) Global cholinergic input simulating attention exerts uniform inhibition onto SACs across glomeruli. The functional impact is shaped by differential connectivity: SACs which have stronger inhibitory connections to OSNs, are more strongly suppressed by the same cholinergic signal, effectively biasing glomerular responses during attentive states.

Animals can use cues to initiate task preparation and amplify relevant #sensory input, but how? This study describes a circuit whereby an attentional cue triggers #cholinergic #forebrain activity, enhancing #olfactory responses (deactivated upon task-proficiency) @plosbiology.org 🧪 plos.io/3VnO1hT

Modeling plasticity dependent selective attention. Schematic of the glomerular network model incorporating leaky-integrate-and-fire (LIF) neurons to simulate odor-driven activity and cholinergic modulation in the olfactory bulb. (i) Diagram showing selective activation of a subset of excitatory olfactory sensory neurons (OSNs, circles) by conditioned stimuli (CS+ or CS−). OSNs form reciprocal connections with inhibitory short axon cells (SACs, small circles with connections). CS+ trials (blue) selectively activate a specific OSN-SAC ensemble, while CS− trials (brown) activate a different subset. Network wiring enables targeted modulation of specific glomeruli based on stimulus identity. (ii) Valence-dependent synaptic changes within the OSN-SAC microcircuit. Differential cholinergic input (blue arrow for CS+, brown arrow for CS−) modulates SAC inhibition, shaping OSN-SAC connectivity via a Hebbian learning rule. Increased inhibition of SACs during CS+ trials promotes disinhibition of OSNs, enhancing their activity, while reduced inhibition during CS− trials maintains higher SAC-mediated suppression, thereby reducing bottom–up activation of SACs. (iii) Global cholinergic input simulating attention exerts uniform inhibition onto SACs across glomeruli. The functional impact is shaped by differential connectivity: SACs which have stronger inhibitory connections to OSNs, are more strongly suppressed by the same cholinergic signal, effectively biasing glomerular responses during attentive states.

Animals can use cues to initiate task preparation and amplify relevant #sensory input, but how? This study describes a circuit whereby an attentional cue triggers #cholinergic #forebrain activity, enhancing #olfactory responses (deactivated upon task-proficiency) @plosbiology.org 🧪 plos.io/3VnO1hT

The efficacy of perampanel as a second-line therapy to midazolam for refractory SE was evaluated in soman-exposed rats.
doi.org/10.1002/epi4...

#epilepsy #ilae #epilepsiaopen #AMPA #antiseizuremedication #cholinergic #organophosphorusnerveagent #pharmacoresistance

Top left: Representative brain confocal stack of dFB-Split>UAS-mCD8GFP. Green, anti-GFP; magenta, anti-nc82. Top right: Representative brain confocal stack of dFB-Split>UAS-Kir2.1.EGFP. The authors observed 23.40 ± 0.75 (n = 5) dFB23E10Ո84C10 neurons in dFB-Split>UAS-Kir2.1.EGFP brains. Green, anti-GFP; magenta, anti-nc82. Bottom left: Representative confocal stack of a female VGlut-AD (84713); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker). Bottom right: Representative confocal stack of a female VGlut-AD (82986); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker).

Sleep regulation in #Drosophila. @sdissel.bsky.social &co show that #cholinergic #neurons in the dorsal fan-shaped body (dFB) play a major role in #sleep modulation in this neurochemically heterogeneous region of the fly brain 🧪 @plosbiology.org plos.io/42uPczp

Top left: Representative brain confocal stack of dFB-Split>UAS-mCD8GFP. Green, anti-GFP; magenta, anti-nc82. Top right: Representative brain confocal stack of dFB-Split>UAS-Kir2.1.EGFP. The authors observed 23.40 ± 0.75 (n = 5) dFB23E10Ո84C10 neurons in dFB-Split>UAS-Kir2.1.EGFP brains. Green, anti-GFP; magenta, anti-nc82. Bottom left: Representative confocal stack of a female VGlut-AD (84713); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker). Bottom right: Representative confocal stack of a female VGlut-AD (82986); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker).

Sleep regulation in #Drosophila. @sdissel.bsky.social &co show that #cholinergic #neurons in the dorsal fan-shaped body (dFB) play a major role in #sleep modulation in this neurochemically heterogeneous region of the fly brain 🧪 @plosbiology.org plos.io/42uPczp

Top left: Representative brain confocal stack of dFB-Split>UAS-mCD8GFP. Green, anti-GFP; magenta, anti-nc82. Top right: Representative brain confocal stack of dFB-Split>UAS-Kir2.1.EGFP. The authors observed 23.40 ± 0.75 (n = 5) dFB23E10Ո84C10 neurons in dFB-Split>UAS-Kir2.1.EGFP brains. Green, anti-GFP; magenta, anti-nc82. Bottom left: Representative confocal stack of a female VGlut-AD (84713); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker). Bottom right: Representative confocal stack of a female VGlut-AD (82986); 23E10-DBD>UAS-mCD8GFP brain. Yellow and red arrows show non-dFB neurons. Green, anti-GFP; magenta, anti-nc82 (neuropile marker).

Sleep regulation in #Drosophila. @sdissel.bsky.social &co show that #cholinergic #neurons in the dorsal fan-shaped body (dFB) play a major role in #sleep modulation in this neurochemically heterogeneous region of the fly brain @plosbiology.org 🧪 plos.io/42uPczp