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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has previously been shown that the neuropeptide galanin plays a role in the age-dependent regulation of hippocampal synaptic plasticity and spatial memory. Here, we further extend these studies by demonstrating that galanin knockout mice also have deficits in an object-in-place spatial memory task. In contrast however, there is no deficit in single item object recognition memory, a memory that depends on perirhinal cortex. Furthermore, in perirhinal cortex slices there are no differences in activity-dependent long-term potentiation or depotentiation, nor in muscarinic receptor-dependent long-term depression between galanin knockout mice and wild-type litter-mates. Therefore, these results suggest that galanin has a differential role in hippocampal-dependent and perirhinal cortex-dependent memory.
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PMID:Galanin regulates spatial memory but not visual recognition memory or synaptic plasticity in perirhinal cortex. 1255 20

(1) The effects on the whole-cell carbachol-induced muscarinic cationic current (mIcat) of antibodies against the alpha-subunits of various G proteins, as well as the effect of a Gbetagamma subunit, were studied in single guinea-pig ileal smooth muscle cells voltage-clamped at -50 mV. Ionized intracellular calcium concentration, [Ca(2+)](i), was clamped at 100 nM using a 1,2-bis(2-aminophenoxyl-ethane-N,N,N',N'-tetraacetic acid)/Ca(2+) mixture. (2) Application of ascending concentrations of carbachol (1-300 micro M) activated mIcat (mean amplitude 0.83 nA at 300 micro M carbachol; EC(50) 8 micro M; Hill slope 1.0). A 20 min or longer intracellular application via the pipette solution of G(i3)/G(o) or G(o) antibodies resulted in about a 70% depression of the maximum response without change in the EC(50) value. In contrast, antibodies against alpha-subunits of G(i1), G(i1)/G(i2), G(i3), G(q)/G(11) or G(s) protein over a similar or longer period did not significantly reduce mIcat. Antibodies to common Gbeta or infusion of the Gbetagamma subunit itself had no effect on mIcat. (3) If cells were exposed briefly to carbachol (50 or 100 micro M) at early times (<3 min) after infusion of antibodies to Galpha(i3)/Galpha(o) or to Galpha(o) had begun, carbachol responses remained unchanged even after 20-60 min; that is, the depression of mIcat by these antibodies was prevented. (4) These data show that Galpha(o) protein couples the muscarinic receptor to the cationic channel in guinea-pig ileal longitudinal smooth muscle and that Gbetagamma is not involved. They also show that prior activation of the muscarinic receptor presumably causes a long-lasting postactivation change of the G protein, which is not reflected in mIcat, but acts to hinder antibody binding.
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PMID:Effects of G-protein-specific antibodies and G beta gamma subunits on the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle cells. 1278 20

We establish the importance of cholinergic neurotransmission to both recognition memory and plasticity within the perirhinal cortex of the temporal lobe. The muscarinic receptor antagonist scopolamine impaired the preferential exploration of novel over familiar objects, disrupted the normal reduced activation of perirhinal neurones to familiar compared to novel pictures, and blocked production of long-term depression (LTD) but not long-term potentiation (LTP) of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for the involvement of cholinergic mechanisms in synaptic plastic processes within perirhinal cortex that are necessary for recognition memory.
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PMID:Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory. 1281 83

Retrograde synaptic signalling has long been recognized as a fundamental feature of neural systems. However, the cellular specificity and functional consequences of fast retrograde communication are not well understood. We have focused our efforts on understanding the role that endocannabinoids play in regulating synaptic inhibition in sensory neocortex. Recent studies have implicated endocannabinoids as the retrograde signalling molecules that underlie depolarization-induced suppression of inhibition, or DSI. This short-term form of presynaptic depression is triggered by postsynaptic depolarization and is likely to play an important role in information processing. In the present study we investigated the cellular and synaptic specificity of endocannabinoid signalling in sensory cortex using whole-cell recordings from layer 2/3 pyramidal neurones (PNs) in acute brain slices. We report that GABAergic interneurones that are depolarized by muscarinic receptor stimulation provided the majority of DSI-susceptible inputs to neocortical PNs. This subclass of interneurones generated large, fast postsynaptic currents in PNs which were transiently suppressed by either postsynaptic depolarization or a brief train of action potentials. Neocortical DSI required activation of the type 1 cannabinoid receptor (CB1R) but not metabotropic glutamate or GABA receptors. Using focal drug application, we found that the DSI-susceptible afferents preferentially synapse on the perisomatic membrane of PNs, and not on the apical dendrites. Together, these results suggest that endocannabinoid-mediated DSI in the cortex can transiently and selectively depress a subclass of PN inputs. Although the physiological implications remain to be explored, this suppression of somatic inhibition may alter the excitability of principal neurones and thereby modulate cortical output.
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PMID:Endocannabinoid signalling selectively targets perisomatic inhibitory inputs to pyramidal neurones in juvenile mouse neocortex. 1474 27

The subiculum is a limbic cortical region that receives inputs from hippocampus and other parahippocampal regions. We used horizontal brain slices to study the modulatory effects of muscarinic receptor activation on excitatory afferent systems of the subiculum. Multiple inputs are preserved in these slices. Carbachol (CCh, applied to the bath) induced a decrease in the field responses (40-50% at 50 microM; 60% at 100 microM) to CA1, presubicular (PreS), and medial entorhinal (MEC) stimulation. Subicular responses to lateral entorhinal (LEC) stimuli were not depressed. The M1 receptor antagonist pirenzepine at 1 microM was sufficient to reverse most of the CCh-induced depression of afferent excitation, but 10 microM concentrations were required to eliminate the CCh-induced firing in the isolated subiculum. A partial reversal of the CCh-induced depression of afferent excitation was achieved by the M2 receptor antagonist methoctramine (1 or 10 microM), but these concentrations did not prevent CCh-induced firing. When CA1 afferents were repetitively activated with submaximal stimuli in the presence of CCh, population excitatory postsynaptic potentials (EPSPs) showed modest summation, but every response was smaller than a corresponding events in normal media. Population spikes, particularly late spikes in a train, showed pronounced facilitation during CCh exposure. The NMDA receptor antagonist CPP (10 microM) prevented facilitation of responses to repetitive stimulation in the presence of carbachol. We conclude that CA1, PreS, and MEC afferents to the subiculum exhibit CCh sensitivity similar to that established for area CA3 afferents to CA1, and LEC afferents to subiculum exhibit CCh resistance. Our data suggest that much of the hippocampal formation circuitry is modulated by CCh and the properties of this modulation can explain some specific firing characteristics of hippocampal formation neurons in "cholinergic" versus "noncholinergic" brain states.
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PMID:Differential modulation by carbachol of four separate excitatory afferent systems to the rat subiculum in vitro. 1539 Jan 73

Respiratory and arousal state control are heritable traits in mice. B6.V-Lep(ob) (ob) mice are leptin deficient and differ from C57BL/6J (B6) mice by a variation in the gene coding for leptin. The ob mouse has morbid obesity and disordered breathing that is homologous to breathing of obese humans. This study tested the hypothesis that microinjecting neostigmine into the pontine reticular nucleus, oral part (PnO), of B6 and ob mice alters sleep and breathing. In B6 and ob mice, neostigmine caused a concentration-dependent increase (P < 0.0001) in percentage of time spent in a rapid eye movement (REM) sleeplike state (REM-Neo). Relative to saline (control), higher concentrations of neostigmine increased REM-Neo duration and the number of REM-Neo episodes in B6 and ob mice and decreased percent wake, percent non-REM, and latency to onset of REM-Neo (P < 0.001). In B6 and ob mice, REM sleep enhancement by neostigmine was blocked by atropine. Differences in control amounts of sleep and wakefulness between B6 and the congenic ob mice also were identified. After PnO injection of saline, ob mice spent significantly (P < 0.05) more time awake and less time in non-REM sleep. B6 mice displayed more (P < 0.01) baseline locomotor activity than ob mice, and PnO neostigmine decreased locomotion (P < 0.0001) in B6 and ob mice. Whole body plethysmography showed that PnO neostigmine depressed breathing (P < 0.001) in B6 and ob mice and caused greater respiratory depression in B6 than ob mice (P < 0.05). Western blot analysis identified greater (P < 0.05) expression of M2 muscarinic receptor protein in ob than B6 mice for cortex, midbrain, cerebellum, and pons, but not medulla. Considered together, these data provide the first evidence that pontine cholinergic control of sleep and breathing varies between mice known to differ by a spontaneous mutation in the gene coding for leptin.
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PMID:C57BL/6J and B6.V-LEPOB mice differ in the cholinergic modulation of sleep and breathing. 1547 96

Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human.
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PMID:Methyl parathion increases neuronal activities in the rat locus coeruleus. 1559 69

The central cholinergic system plays a crucial role in synaptic plasticity and spatial attention; however, the roles of the individual cholinergic receptors involved in these activities are not well understood at present. In the present study, we show that acetylcholine (ACh) can facilitate or depress synaptic transmission in occipital slices of mouse visual cortex. The precise nature of the ACh effects depends on the ACh concentration, and is input specific, as shown by stimulating different synaptic pathways. Pharmacological blockade of muscarinic receptor (mAChR) subtypes and the use of M1-M5 mAChR-deficient mice showed that specific mAChR subtypes, together with the activity of the cholinesterases (ChEs), mediate facilitation or depression of synaptic transmission. The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli.
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PMID:Acetylcholine modulates cortical synaptic transmission via different muscarinic receptors, as studied with receptor knockout mice. 1591 9

In depressed patients, sleep undergoes marked alterations, especially sleep onset insomnia, sleep fragmentation, and disturbances of the Rapid Eye Movement (REM) sleep. Abnormalities of rest-activity rhythms and of hypothalamic-pituitary-adrenocortical function have also been described in these patients. In the present study, we examined the presence of such abnormalities in a recently developed line of mice (Helpless mice-H) that exhibit depression-like behaviors in validated tests, compared to the nonhelpless (NH) line derived from the same colony. Experiments were essentially carried out in females for which previous studies showed marked differences between H and NH lines. Compared to NH mice, the H line exhibited (i) lower basal locomotor activity, (ii) sleep fragmentation, shift towards lighter sleep stages, and facilitation of REM sleep reflected by increased amounts and decreased latency, (iii) larger response to the REM sleep promoting effect of muscarinic receptor stimulation (by arecoline). In contrast, H and NH mice were equally responsive to the REM sleep inhibitory effect of 5-HT1A receptor stimulation (by 8-OH-DPAT). In addition, a deficiency in delta power enhancement after sleep deprivation was observed in the H group, and acute immobilization stress in this group failed to elicit a REM sleep rebound and was associated with a long-lasting raise in serum corticosterone levels. These results further validate H mice as a depression model and suggest they might be of particular interest for investigating the neurobiological mechanisms and possibly genetic substrates underlying sleep alterations associated with depression.
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PMID:Homeostatic regulation of sleep in a genetic model of depression in the mouse: effects of muscarinic and 5-HT1A receptor activation. 1629 25

We studied the cholinergic modulation of glutamatergic transmission between neighboring layer 5 regular-spiking pyramidal neurons in somatosensory cortical slices from young rats (P10-P26). Brief bath application of 5-10 microM carbachol, a nonspecific cholinergic agonist, decreased the amplitude of evoked unitary excitatory postsynaptic potentials (EPSPs). This effect was blocked by 1 microM atropine, a muscarinic receptor antagonist. Nicotine (10 microM), in contrast to carbachol, reduced EPSPs in nominally magnesium-free solution but not in the presence of 1 mM Mg+2, indicating the involvement of NMDA receptors. Likewise, when the postsynaptic cell was depolarized under voltage clamp to allow NMDA receptor activation in the presence of 1 mM Mg+2, synaptic currents were reduced by nicotine. Nicotinic EPSP reduction was prevented by the NMDA receptor antagonist D-AP5 (50 microM) and by the nicotinic receptor antagonist mecamylamine (10 microM). Both carbachol and nicotine reduced short-term depression of EPSPs evoked by 10 Hz stimulation, indicating that EPSP reduction happens via reduction of presynaptic glutamate release. In the case of nicotine, several possible mechanisms for NMDAR-dependent EPSP reduction are discussed. As a result of NMDA receptor dependence, nicotinic EPSP reduction may serve to reduce the local spread of cortical excitation during heightened sensory activity.
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PMID:Nicotinic and muscarinic reduction of unitary excitatory postsynaptic potentials in sensory cortex; dual intracellular recording in vitro. 1642 Nov 99


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