Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus.

Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus.

PLoS One. 2013; 8(5): e63662
Kobayashi K, Ikeda Y, Asada M, Inagaki H, Kawada T, Suzuki H

The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This “dematuration” is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions. HubMed – depression


Some Preliminary Notes on an Empirical Test of Freud’s Theory on Depression.

Front Psychol. 2013; 4: 158
Desmet M

A review of the literature indicates that empirical researchers have difficulty translating Freud’s theory on depression into appropriate research questions and hypotheses. In their attempt to do so, the level of complexity in Freud’s work is often lost. As a result, what is empirically tested is no more than a caricature of the original theory. To help researchers avoid such problems, this study presents a conceptual analysis of Freud’s theory of depression as it is presented in Mourning and Melancholia (Freud, 1917). In analyzing Freud’s theory on the etiology of depression, it is essential to differentiate between (1) an identification with the satisfying and frustrating aspects of the love object, (2) the inter- and an intrapersonal loss of the love object, and (3) conscious and unconscious dynamics. A schematic representation of the mechanism of depression is put forward and a research design by which this schema can be empirically investigated is outlined. HubMed – depression


Issues in the Management of Acute Agitation: How Much Current Guidelines Consider Safety?

Front Psychiatry. 2013; 4: 26
Pacciardi B, Mauri M, Cargioli C, Belli S, Cotugno B, Di Paolo L, Pini S

Agitated behavior constitutes up to 10% of emergency psychiatric interventions. Pharmacological tranquilization is often used as a valid treatment for agitation but a strong evidence base does not underpin it. Available literature shows different recommendations, supported by research data, theoretical considerations, or clinical experience. Rapid tranquilization (RT) is mainly based on parenteral drug treatment and the few existing guidelines on this topic, when suggesting the use of first generation antipsychotics and benzodiazepines, include drugs with questionable tolerability profile such as chlorpromazine, haloperidol, midazolam, and lorazepam. In order to systematically evaluate safety concerns related to the adoption of such guidelines, we reviewed them independently from principal diagnosis while examining tolerability data for suggested treatments. There is a growing evidence about safety profile of second generation antipsychotics for RT but further controlled studies providing definitive data in this area are urgently needed. HubMed – depression


Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression.

Front Comput Neurosci. 2013; 7: 59
Miller P

Randomly connected recurrent networks of excitatory groups of neurons can possess a multitude of attractor states. When the internal excitatory synapses of these networks are depressing, the attractor states can be destabilized with increasing input. This leads to an itinerancy, where with either repeated transient stimuli, or increasing duration of a single stimulus, the network activity advances through sequences of attractor states. We find that the resulting network state, which persists beyond stimulus offset, can encode the number of stimuli presented via a distributed representation of neural activity with non-monotonic tuning curves for most neurons. Increased duration of a single stimulus is encoded via different distributed representations, so unlike an integrator, the network distinguishes separate successive presentations of a short stimulus from a single presentation of a longer stimulus with equal total duration. Moreover, different amplitudes of stimulus cause new, distinct activity patterns, such that changes in stimulus number, duration and amplitude can be distinguished from each other. These properties of the network depend on dynamic depressing synapses, as they disappear if synapses are static. Thus, short-term synaptic depression allows a network to store separately the different dynamic properties of a spatially constant stimulus. HubMed – depression


Mathematical analysis and algorithms for efficiently and accurately implementing stochastic simulations of short-term synaptic depression and facilitation.

Front Comput Neurosci. 2013; 7: 58
McDonnell MD, Mohan A, Stricker C

The release of neurotransmitter vesicles after arrival of a pre-synaptic action potential (AP) at cortical synapses is known to be a stochastic process, as is the availability of vesicles for release. These processes are known to also depend on the recent history of AP arrivals, and this can be described in terms of time-varying probabilities of vesicle release. Mathematical models of such synaptic dynamics frequently are based only on the mean number of vesicles released by each pre-synaptic AP, since if it is assumed there are sufficiently many vesicle sites, then variance is small. However, it has been shown recently that variance across sites can be significant for neuron and network dynamics, and this suggests the potential importance of studying short-term plasticity using simulations that do generate trial-to-trial variability. Therefore, in this paper we study several well-known conceptual models for stochastic availability and release. We state explicitly the random variables that these models describe and propose efficient algorithms for accurately implementing stochastic simulations of these random variables in software or hardware. Our results are complemented by mathematical analysis and statement of pseudo-code algorithms. HubMed – depression