scholarly journals Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

2020 ◽  
Vol 21 (8) ◽  
pp. 2734 ◽  
Author(s):  
Giuseppe Di Giovanni ◽  
Laura Clara Grandi ◽  
Ernesto Fedele ◽  
Gergely Orban ◽  
Agnese Salvadè ◽  
...  
Keyword(s):  
Neuronal Firing ◽  
Phase Correlation ◽  
Gamma Aminobutyric Acid ◽  
Clear Cut ◽  
Motor Information ◽  
Chronic Denervation ◽  
6 Hydroxydopamine ◽  
Motor Thalamus ◽  
Shed Light ◽  
Thalamic Function

The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.

Synaptic Properties of Sensory Thalamus

2021 ◽  
Author(s):  
Martha E. Bickford
Keyword(s):  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Conceptual Frameworks ◽  
Thalamic Nuclei ◽  
Dorsal Thalamus ◽  
Synaptic Terminals ◽  
Thalamic Function

Detailed studies of thalamic circuits have revealed many features that are shared across nuclei. For example, glutamatergic inputs to the thalamus can be placed into three categories based on the size of the synaptic terminals they form, their synaptic arrangements, and the postsynaptic responses they elicit. Remarkably, these three categories can be identified in most sensory nuclei of the dorsal thalamus. Likewise, in most sensory thalamic nuclei, circuits that release the neurotransmitter gamma aminobutyric acid (GABA) can be placed into two general categories based on their dendritic or axonal origins. Finally, similar cholinergic circuits have been identified across thalamic nuclei. The ultimate goal of examining the shared versus diverse features of thalamic circuits is to identify fundamental modules, mechanisms, and/or conceptual frameworks, in order to decipher thalamic function.

scholarly journals Johan Ernst Gunnerus and the Quest for the Soul in the Eighteenth Century

2015 ◽  
Vol 12 ◽  
pp. 132-160
Author(s):  
Friedemann Stengel
Keyword(s):  
Eighteenth Century ◽  
Present Article ◽  
Salient Feature ◽  
Political Scientist ◽  
Clear Cut ◽  
The Enlightenment ◽  
European Culture ◽  
Interdisciplinary Nature ◽  
Immortality Of The Soul ◽  
Shed Light

The Norwegian bishop, theologian, philosopher, political scientist, and naturalist, Johan Ernst Gunnerus, can be regarded as one of the most significant proponents of continental European culture in eighteenth-century Norway. The eighteenth-century debate on the meaning and locus of the soul, considered the most central scholarly debate of the ‘Century of Enlightenment’, clearly exemplifies Gunnerus’ own entanglement in contemporaneous philosophical and theological debates. While delineating his position within it, the present article seeks to shed light on its crucial dimensions and arguments, while also illuminating its impact on the transmission of traditional Christian ideas. Theological-philosophical concepts underwent dramatic transformations – in particular, on the question of the immortality of the soul – that also extended to anthropology, eschatology and the divine doctrine. Positioning Gunnerus within this debate demonstrates the interdisciplinary nature of scholarly interactions on topics that today might be deemed purely theological. Their vigorous resistance to dogma and barriers to autonomous thinking form a salient feature of the Enlightenment era. In contextualizing Gunnerus’ doctrine on the soul, it becomes clear that classifying theologies and philosophies according to clear-cut categories like ‘Enlightenment’, ‘Pietism’, or ‘Esotericism’, prunes the complexity of the debates and implicates far-reaching perspectives of the Enlightenment discourse in notions generated in the centuries thereafter.

GABAergic effects on respiratory neuronal discharge during opossum development

1993 ◽  
Vol 264 (2) ◽  
pp. R331-R336
Author(s):  
J. P. Farber
Keyword(s):  
Gabaa Receptors ◽  
Breathing Pattern ◽  
Age Groups ◽  
Neuronal Firing ◽  
Respiratory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Firing Rates ◽  
Medullary Respiratory Neurons ◽  
Expiratory Neurons ◽  
Gabaa Antagonist

Changes in breathing pattern between immature and adult animals could be due in part to changing postsynaptic sensitivity to particular neurotransmitters by respiratory neurons and/or to the fate of these neurotransmitters after release. To probe for such effects, gamma-aminobutyric acid (GABA) and the GABAA antagonist, bicuculline, were pressure injected by micropipette in very small volumes (approximately 25 pl) near identified medullary respiratory neurons in Inactin-anesthetized adult and suckling opossums. At a concentration of 10 mM, GABA induced suppression of respiratory neurons firing in animals from about 3 wk of age (the youngest animals tested) onward, with the largest responses occurring in adults. For those age groups tested with 0.5 and 50 mM GABA, shorter and longer responses, respectively, were observed. Bicuculline increased the discharge of respiratory units at all ages tested, but responses normalized to initial firing rates did not systematically differ between sucklings down to 4 wk of age and adults. Bicuculline also influenced the onset and cessation of firing in both inspiratory and expiratory neurons. Discharge of respiratory neurons in immature suckling opossums is characterized by few spikes and low firing rates with each breath. However, recovery of neuronal firing from an exogenous load of GABA and release of neuronal firing after antagonism of GABAA receptors does not show a developmental pattern that would implicate GABA as the crucial mediator of these effects.

Unilateral Dopamine Denervation Blocks Corticostriatal LTP

1999 ◽  
Vol 82 (6) ◽  
pp. 3575-3579 ◽  
Author(s):  
Diego Centonze ◽  
Paolo Gubellini ◽  
Barbara Picconi ◽  
Paolo Calabresi ◽  
Patrizia Giacomini ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Long Term Potentiation ◽  
Membrane Properties ◽  
High Frequency Stimulation ◽  
Cortex Lesion ◽  
Electrophysiological Recordings ◽  
Motor Information ◽  
6 Hydroxydopamine

The nigrostriatal dopaminergic projection is crucial for the striatal processing of motor information received from the cortex. Lesion of this pathway in rats causes locomotor alterations that resemble some of the symptoms of Parkinson's disease and significantly alters the excitatory transmission in the striatum. We performed in vitro electrophysiological recordings to study the effects of unilateral striatal dopamine (DA) denervation obtained by omolateral nigral injection of 6-hydroxydopamine (6-OHDA) in the formation of corticostriatal long-term potentiation (LTP). Unilateral nigral lesion did not affect the intrinsic membrane properties of striatal spiny neurons. In fact, these cells showed similar pattern of firing discharge and current-voltage relationship in denervated striata and in naive controlateral striata. Moreover, excitatory postsynaptic potentials (EPSPs) evoked by stimulating corticostriatal fibers and recorded from DA-denervated slices showed a pharmacology similar to that observed in slices obtained from controlateral intact striata. Conversely, in magnesium-free medium, high-frequency stimulation (HFS) of corticostriatal fibers produced LTP in slices from nondenervated striata but not in slices from 6-OHDA–denervated rats. After denervation, in fact, no significant changes in the amplitude of extra- and intracellular synaptic potentials were recorded after the conditioning HFS. The absence of corticostriatal LTP in DA-denervated striata might represent the cellular substrate for some of the movement disorders observed in Parkinson's disease.

scholarly journals Circadian rhythm in cortical chloride homeostasis underpins variation in network excitability

2021 ◽  
Author(s):  
Enrico Pracucci ◽  
Rob Graham ◽  
Laura S Alberio ◽  
Gabriele Nardi ◽  
Olga Cozzolino ◽  
...  
Keyword(s):  
Chloride Concentration ◽  
Pyramidal Cells ◽  
Surface Expression ◽  
Neuronal Firing ◽  
Gamma Aminobutyric Acid ◽  
Cortical Networks ◽  
Night Time ◽  
Adult Mice ◽  
Circadian Fluctuation ◽  
The Stability

The main inhibitory synaptic currents, gated by gamma-aminobutyric acid (GABA), are mediated by Cl--conducting channels1-3, and are therefore sensitive to changes in the chloride electrochemical gradient. GABAergic activity dictates the neuronal firing range4,5 and timing6-9, which in turn influences the rhythms of the brain, synaptic plasticity, and flow of information in neuronal networks7,10-12. The intracellular chloride concentration [Cl-]i 13is, therefore, ideally placed to be a regulator of neuronal activity. Chloride levels13 have been thought to be stable in adult cortical networks, except when associated with pathological activation14-17. Here, we used 2-photon LSSmClopHensor imaging14, in anaesthetized young adult mice, to show a large physiological circadian fluctuation of baseline [Cl-] inside pyramidal cells, equating to an ~15mV positive shift in ECl at times when mice are typically awake (midnight), relative to when they are usually asleep (midday). The change in pyramidal [Cl-]i alters the stability of cortical networks, as demonstrated by a greater than 3-fold longer latency to seizures induced by 4-aminopyridine at midday, compared to midnight. Importantly, both [Cl-]i and latency to seizure, in night-time experiments, were shifted in line with day-time measures, by inhibition of NKCC1. The redistribution of [Cl-]i reflects circadian changes in surface expression and phosphorylation states of the cation-chloride-co-transporters, KCC2 and NKCC1, leading to a greatly reduced chloride-extrusion capacity at night (awake period). Our data show how changes in the biochemical state of neurons may be transduced into altered brain states.

The Story of the Button on the Jacket—Substances of Very High Concern in Complex Products

2011 ◽  
Vol 8 (4) ◽  
pp. 353-371
Author(s):  
Marianne Hoppenbrouwers
Keyword(s):  
Supply Chain ◽  
The Other ◽  
Legal Text ◽  
Complex Products ◽  
Clear Cut ◽  
Advantages And Disadvantages ◽  
High Concern ◽  
Reach Regulation ◽  
Very High ◽  
Shed Light

AbstractSubstances of Very High Concern (SVHC) are subject to specific rules in the REACH regulation. For example, once the concentration of SVHCs in articles exceeds 0,1% weight by weight notification to ECHA and communication in the supply chain is obligatory. However, many products are in fact complex articles, consisting of many articles sometimes with SVHCs. The calculation of the concentration of SVHC in complex articles is open for interpretation due to the lack of clear definitions in the legal text of REACH. Two formulas, one defended by ECHA and the other by six Member States exist. Each has its advantages and disadvantages. The choice is not clear cut. is article tries to shed light on the issues and gives a beginning of a solution.

Sympatholytic effect of tricyclic antidepressants: site and mechanism of action in anesthetized rats

1995 ◽  
Vol 268 (6) ◽  
pp. R1429-R1441 ◽  
Author(s):  
D. Huangfu ◽  
W. B. Goodwin ◽  
P. G. Guyenet
Keyword(s):  
Adrenergic Receptor ◽  
Tricyclic Antidepressants ◽  
Aminobutyric Acid ◽  
Ventrolateral Medulla ◽  
Gamma Aminobutyric Acid ◽  
Uptake Inhibition ◽  
Noradrenergic Fibers ◽  
6 Hydroxydopamine ◽  
Serotonin Uptake Inhibition ◽  
Nerve Discharge

Intravenous desipramine (DMI) and amitriptyline, but not fluoxetine, dose dependently inhibited splanchnic sympathetic nerve discharge (sSND; -64 +/- 3% after 4 mg/kg iv DMI, 172 ng/ml plasma) in urethan-anesthetized debuffered rats. Inhibition was reversed or prevented by microinjection of the alpha 2-adrenergic receptor (alpha 2-AR) antagonist 2-methoxyidazoxan (MOI) into the rostral ventrolateral medulla (RVLM, 1 nmol/side). sSND inhibition (-58 +/- 12%) by baclofen (8 mg/kg iv, a gamma-aminobutyric acid-B receptor agonist) was unaffected by MOI. MOI alone raised sSND 46 +/- 9%. Microinjection of 6-hydroxydopamine into the RVLM (2 micrograms/side, 10-13 days, to destroy noradrenergic terminals) did not change the effect of intravenous DMI or MOI on sSND. Slow-firing presympathetic neurons of the RVLM were activated by iontophoretic MOI (26 +/- 4%) and inhibited by 4 mg/kg iv DMI (-44 +/- 12%, effect reversed by alpha 2-AR antagonists iv). We interpret these findings as follows: 1) alpha 2-ARs in the RVLM are activated at rest, probably by catecholamines released by C1 adrenergic cells, 2) this activation reduces sSND, 3) DMI and amitriptyline reduce sSND by increasing alpha 2-AR activation in the RVLM, and 4) these effects are due to neither serotonin uptake inhibition nor blockade of norepinephrine uptake by noradrenergic fibers.

Involvement of Human Thalamic Neurons in Internally and Externally Generated Movements

2004 ◽  
Vol 91 (2) ◽  
pp. 1085-1090 ◽  
Author(s):  
M. L. MacMillan ◽  
J. O. Dostrovsky ◽  
A. M. Lozano ◽  
W. D. Hutchison
Keyword(s):  
Visual Cues ◽  
Specific Activity ◽  
Premotor Cortex ◽  
Neuronal Firing ◽  
Button Press ◽  
Neural Pathways ◽  
Means Testing ◽  
Sequential Movements ◽  
Motor Thalamus ◽  
Post Hoc

Several anatomical studies support the existence of recurrent neural pathways from cortical motor areas to the thalamus via basal ganglia and back to the cortex. Neuronal responses to internally and externally generated sequential movements have been studied in the motor and premotor cortex of monkeys, but the involvement of subcortical motor structures such as the thalamus have not been studied in monkeys or humans. We examined the activity of neurons during a sequential button press task in motor thalamus of parkinsonian as well as chronic pain patients undergoing implantation of deep brain stimulating electrodes. Single and dual microelectrode recordings were carried out during an internally generated task with a memorized sequence (MEM) and an externally driven task with the sequence given during task performance (follow). Average histograms of neuronal firing were constructed for each task and aligned with respect to visual cues (ready, go) or button presses (P1, P2, P3). Sequential movements were monitored with surface electromyography and hand accelerometry, and cell responses were divided into movement-defined epochs for ANOVA and post hoc means testing. Of 52 neurons tested, 31 were found to have task-related responses and 10 were task-selective with 4 responding preferentially to MEM and 7 responding preferentially to follow (1 was both). Complex responses were found including preparatory, delay period, and phase- and task-specific activity. These kinds of responses suggest a role of the thalamus in both internally and externally cued arms movement and provide some evidence for a role in sequential movements.

Dopaminergic modulation of rod pathway signals does not affect the scotopic ERG of cat at dark-adapted threshold

1993 ◽  
Vol 70 (4) ◽  
pp. 1681-1691 ◽  
Author(s):  
F. Naarendorp ◽  
P. F. Hitchock ◽  
P. A. Sieving
Keyword(s):  
Absolute Threshold ◽  
Experimental Manipulation ◽  
Aminobutyric Acid ◽  
Dopamine Antagonist ◽  
Gamma Aminobutyric Acid ◽  
Dopaminergic Cells ◽  
Threshold Response ◽  
6 Hydroxydopamine ◽  
Rod Pathway

1. Two rod-driven electroretinogram (ERG) components were recorded to monitor scotopic retinal signals during experimental manipulation of dopamine and gamma-aminobutyric acid (GABA) in normal cat eyes and in eyes pretreated with 6-hydroxydopamine (6-OHDA). The scotopic threshold response (STR) was elicited near absolute threshold to monitor signals traversing the rod pathway near quantal threshold; scotopic PII, which normally begins approximately 2 log units higher, was also monitored. Responses were evaluated by V-log I curves and criterion amplitudes after intravitreal drug injections into intact eyes in vivo. The depletion of dopaminergic cells by pretreating with 6-OHDA was confirmed histologically by immunocytochemical methods. 2. Dopamine abolished the STR and markedly decreased PII in the normal eye. Both 6-OHDA pretreatment and application of the dopamine antagonist, haloperidol, increased the STR amplitudes, but only for stimuli beginning 2 log units above threshold; PII amplitude also was increased. However, neither 6-OHDA pretreatment nor haloperidol affected the STR near absolute threshold. 3. Both GABA and bicuculline suppressed the STR in the normal eye. However, when applied to eyes pretreated with 6-OHDA or concurrent with haloperidol, bicuculline enhanced the STR. GABA enhanced the PII amplitude in the normal eye but had no effect in eyes pretreated with 6-OHDA or in the presence of haloperidol. 4. These results suggest that 1) dopaminergic activity modulates signals in the rod pathway at higher stimulus intensities but not near absolute threshold and 2) GABA can affect the scotopic PII component by acting through dopaminergic cells in the dark-adapted retina.

Influence of GABAergic mechanisms on baroreceptor inputs to nucleus tractus solitarii of rats

1996 ◽  
Vol 271 (3) ◽  
pp. H931-H936 ◽  
Author(s):  
P. Ruggeri ◽  
C. E. Cogo ◽  
V. Picchio ◽  
C. Molinari ◽  
R. Ermirio ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Cardiac Cycle ◽  
Great Majority ◽  
Firing Frequency ◽  
Significant Inhibition ◽  
Neuronal Firing ◽  
Nucleus Tractus Solitarii ◽  
Gabab Receptors ◽  
Spontaneous Discharge ◽  
Gamma Aminobutyric Acid

The firing frequency of baroreceptive neurons in the nucleus tractus solitarii (NTS) during microiontophoretic application of muscimol, a gamma-aminobutyric acid (GABA)A agonist, or baclofen, a GABAB agonist, was monitored in anesthetized rats. Muscimol decreased the spontaneous discharge of 69 of 73 (94.5%) NTS baroreceptive neurons without affecting the remaining four neurons (5.5%). The statistical comparison on a bin-by-bin basis of the peri-R wave interval histograms of the discharge of each NTS neuron showed that the inhibitory action of muscimol was always exerted on the whole neuronal discharge independently of its correlation to the cardiac cycle. Baclofen inhibited 60 of 73 (82.2%) NTS neurons without affecting the remaining 13 neurons (17.8%). In 31 of 60 (51.7%) neurons inhibited by baclofen, this substance significantly affected only pulse-synchronous peaks of neuronal discharge without significant inhibition of the neuronal firing between cardiac cycle-related peaks. Fifty-eight of 73 (79.5%) NTS neurons studied were inhibited by both muscimol and baclofen, 11 neurons (15%) only by muscimol, 2 neurons (2.7%) only by baclofen, and 2 neurons (2.7%) were unaffected by both substances. These results demonstrate that both GABAA and GABAB receptors mediate inhibition of the spontaneous discharge in the great majority of the NTS baroreceptive neurons studied and suggest different functions of the two types of GABA receptors in influencing baroreceptor inputs to the NTS.

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