Time and the dopamine hypothesis.
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Brain↗
Biomedical subjects
J B Aldenhoff
Publications and source records attributed to J B Aldenhoff.
A current source density analysis of field potentials evoked in slices of visual cortex.
The method of one-dimensional current source density (CSD) analysis was applied to field potentials recorded from 350 microns thick slices of the primary visual cortex of rats and cats. Field potentials were elicited by stimulation of the white matter and recorded along trajectories perpendicular to the cortical layers at spatial intervals of 25 to 50 microns. The resulting CSD distributions resembled closely those recorded from the cat visual cortex "in vivo". The responses with the shortest latency were distinct sinks in layers IV and VI probably reflecting monosynaptic EPSP's from specific thalamic afferents. From layer IV activity was relayed along three major routes: 1. to the supragranular layers via strong local connections to layer III and from there via both short and long range connections to layer II, 2. to targets within layer IV, and 3. to layer V. The source distributions suggest that the projections to layers III and II terminate on the proximal and distal segments, respectively, of apical dendrites of layer III pyramidal cells while the projection to layer V contacts the apical dendrites of layer VI pyramidal cells. These results indicate that all the excitatory pathways that are detectable with the CSD technique in the "in vivo" preparation remain intact in 350 micron thick cortical slices. However, in the slice paired pulse stimulation did not lead to a depression of the response to the second stimulus while this is the case "in vivo". This might be due to reduced inhibition in the slice which has been reported by several authors.
Age Factors↗
Does corticotropin releasing factor act via a calcium-dependent mechanism?
The widespread distribution of CRF in the brain suggests a possible role of this peptide as a neuromodulator. An interaction with calcium-dependent conductances, as observed in hippocampal slices, could explain the action of CRF in different brain structures. In the present study, the calcium antagonist, verapamil, was found to block the excitatory action of CRF on neuronal discharge activity. This supports the hypothesis that CRF blocks a calcium-dependent potassium conductance, which represents a resting component of neuronal activity, thereby enhancing ion fluxes into the cell.
Action Potentials↗
The effects of verapamil on the locomotor-activating properties of corticotropin releasing factor (CRF) in the rat.
CRF was administered to rats following intracerebroventricular administration of the calcium antagonist verapamil. Treatment with verapamil elicited biphasic dose-response effects on rat locomotor activity: doses equimolar to CRF treatment slightly increased CRF-stimulated locomotion, while doses of verapamil ten times greater slightly depressed CRF-stimulated locomotion. These results suggest that CRF-stimulated locomotion, unlike other effects of CRF, is not mediated in a simple way by processes dependent on neuronal calcium influx.
Animals↗
Antimanic effects of the calcium-antagonist D600. A double-blind placebo-controlled study.
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Adult↗
Lithium slows neuronal calcium regulation in the snail Helix pomatia.
Steady-state and transient changes in intracellular calcium concentrations ([Ca2+]i) of snail neurons (Helix pomatia) were measured by the Ca2+ indicator Arsenazo(III) following manipulation of the extracellular concentration of lithium chloride (LiCl). Application of LiCl in concentrations equivalent to those used in the treatment of manic-depressive illness produces slowing in Ca2+ reequilibration after Ca2+-influx during depolarization, concomitantly with steady-state elevation of [Ca2+]i of about 100 nM, suggesting a change in Ca2+ reequilibration as a prominent action of LiCl. This mechanism may be relevant to the therapeutic effects of LiCl.
Animals↗
[Lithium and calcium-dependent cell functions. The contribution of a membrane physiology approach in explaining the therapeutic effects of lithium].
The action of lithium on cellular calcium regulation has been observed in snail neurons using electrophysiological methods. Recently, calcium-dependent mechanisms are thought to play a central role in the integrative functions of the CNS. The coupling between humoral and electrical effects of neurons by calcium iones appears to be especially interesting in respect of the clinical actions of lithium. Here we discuss clinical and experimental studies considering the question if the well known effects of lithium therapy could be produced by an action of lithium on the calcium regulation of nerve cells.
Animals↗
Stimulation of a sodium influx by cAMP in Helix neurons.
Brief pressure injections of aqueous solutions of cAMP in identified neurons of Helix pomatia caused depolarizations which lasted for tens of seconds. In voltage-clamped neurons an inward current of similar duration was induced which saturated at 10 microA/cm2 cell surface. In the range of negative membrane potentials with little voltage-dependent activation, this current was not accompanied by a change in membrane conductance. The inward current was not produced by injection of ATP, ADP, adenosine, inosine or cGMP. cAMP derivatives produced longer-lasting effects. Prolongation of the inward current was also observed after inhibition of the phosphodiesterase by IBMX. Drugs which block active transport had no effect on the response to cAMP injection. The inward current depended on extracellular sodium, and was maximal when all other mono- and divalent cations were replaced by Na+. The cAMP-induced current was accompanied by a transient increase in [Na+]i, but there was no change in [Cl-]i. Li+ could largely substitute for Na+; Ca2+ was less effective. Addition of Mg2+ or Ca2+ to solutions containing a high Na+-concentration inhibited the response. Internal acidification with HCl reversibly enhanced the inward current. These data indicate that the depolarizing effect of cAMP can be accounted for by an inward movement of Na-ions, and that the effect is augmented by H+-ions.
1-Methyl-3-isobutylxanthine↗
Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons.
Corticotropin releasing factor in concentrations of 15 to 250 nanomoles per liter increased the spontaneous discharge frequency and decreased the size of hyperpolarizations after burst discharges in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Concentrations greater than 250 nanomoles per liter also depolarized the cells. These excitatory actions of corticotropin releasing factor may involve a novel calcium-dependent process.
Action Potentials↗
[The effect of lithium on calcium-dependent processes in nerve cells. Attempt at an explanation for therapeutic observations based on membrane physiologic examinations].
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Animals↗
Regional cerebral blood flow in depression: associations with psychopathology.
Regional cerebral blood flow (rCBF) was measured during rest and cognitive activation in 21 patients with a major depressive episode and 21 healthy subjects. Depressive patients had significantly lower rCBF during rest in the right global, frontal, parietal, occipital and temporal regions and in the left global and frontal regions. During mental activation patients showed significantly lower values in all right and left parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the parietal regions. rCBF was correlated with the scores of the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Melancholia Scale (BRMS), the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A). The most significant negative correlations were obtained with the BPRS. Correlation analyses between each single item of the BPRS and CBF values revealed the strongest associations between emotional withdrawal and decreased CBF. Patients with 'reactive' features had higher CBF than patients without 'reactive' symptoms. Only patients without 'reactive' symptoms had a lower CBF than controls. 'Endogenous' features had no impact on CBF.
Adult↗
Reduced olfactory performance in patients with major depression.
The aim of the present study is to investigate olfactory sensitivity and odor evaluations in a homogeneous sample of unipolar depressive patients using pure olfactory odors. Twenty-four in-patients with major depressive disorder (MDD) were investigated during their acute depressive phase. Eighteen of them participated a second time after successful treatment. A group of healthy subjects, matched by age, sex, and smoking behavior, served as a control. Olfactory sensitivity, as measured by threshold tests, was strongly reduced in patients with severe depression. Additional correlative analyses revealed that the lowered sensitivity could partly be predicted by high depression scores. After successful medical treatment, these sensitivity differences were reduced and did not reach the significance level. The subjective odor evaluations (valence and intensity ratings) were not markedly changed in general. The results reveal that olfactory performance in MDD patients is reduced at an early perceptional level of stimulus processing. It is discussed whether this effect can be attributed to the close functional connection between the main olfactory bulb and the amygdala.
Adult↗
Altered Ca(2+)-homeostasis in single T-lymphocytes of depressed patients.
After stimulation of T-lymphocytes from healthy volunteers with the mitogen phytohemagglutinin (PHA) 40% of the cells exhibit an oscillatory increase in intracellular calcium concentration ([Ca2+]i). During depression the number of cells responding to PHA is reduced to 20%. These cells show a marked decrease in [Ca2+]i-reaction to stimulation and flattened oscillations. This reduction of mitogen-induced Ca2+ signals in T-cells of depressed patients appears to be a reliable state marker in depressive illness and is reversed upon successful treatment with interpersonal psychotherapy (IPT).
Adult↗
Excitability and susceptibility of the brain's electrical activity during sleep: an analysis of late components of AEPs and VEPs.
We investigated ten healthy male subjects and measured late components of AEPs and VEPs during sleep. According to Rechtschaffen and Kales (1968) we performed an off-line scoring procedure of sleep-EEG and averaged the AEPs and VEPs of five different periods, corresponding to sleep stages I, II, III, IV and REM. From the averaged evoked potentials we computed the amplitude-frequency-characteristic (AFC) of the brain (Basar, 1980) during different sleep stages. These AFCs characterize transfer properties of an oscillating system. A comparison of different AFCs has shown that the excitability of the brain depicts a clear alpha resonance during stage I, a pronounced delta resonance during stages II, III and IV, and a theta resonance during REM sleep. A comparison of these results from linear system theory with the nonlinear dynamical behavior of the CNS was performed.
Adult↗