Influence of Inter- and Intra-Synaptic Factors on Information Processing in the Brain

Editorial

21 May 2019

Editorial: Influence of Inter- and Intra-Synaptic Factors on Information Processing in the Brain

Vito Di Maio

and

Jean-Marie C. Bouteiller

2,114 views

1 citations

Editors

Vito Di Maio

Institute of Applied Sciences and Intelligent Systems, Department of Physical Sciences and Technologies of Matter, National Research Council (CNR)

Jean-Marie Charles Bouteiller

University of Southern California

Impact

Time series of the overlap mμ(t) for some representative cases of the system dynamical behavior, corresponding to κ∞ = 20 and to P = 5, 10, 15, and 20, respectively from (A–D). In each composite panel, we illustrate the behavior of the system on for 4 points of the (T, α) space, as indicated by pink starts in the corresponding phase diagrams of Figure 2. Namely, (A) is for the points (0.7, 0.3), (0.9, 0.3), (0.3, 1.1), (1.1, 1.1); (B) is for (0.3, 0.3), (0.9, 0.3), (0.3, 1.1), (1.1, 1.1); and finally (C,D) are for the points (0.1, 0.3), (0.9, 0.3), (0.3, 1.1), (1.1, 1.1). We have selected slightly different points for each P so as to show an example of the oscillatory behavior in each case, and the region of its appearance depends on P. Results are for N = 1, 600.

Original Research

16 April 2019

How Memory Conforms to Brain Development

Ana P. Millán

, 1 more and

Joaquín Marro

5,479 views

16 citations

Activation states of the bistable molecular switch model. (A) The model's potential function, U(x), visually describes the tendency for solutions to settle around one of two equilibrium points (x*), where the rate of change of switch activation, f(x), is 0 (parameters, r = 0.52 and c = 0.04). To the left of the stable equilibria (black circles), f(x)>0 (green), and to the right, f(x) < 0 (blue), which forces perturbations to settle back into those states. Conversely, the sign of f(x) is reversed on both sides of the unstable equilibrium (red circle), such that tiny perturbations push the switch away, toward either stable state. (B) As r or c change, f(x) changes and can result in the loss of bistability. (i) To illustrate, r is fixed as the input c is varied: small values only support low activation, but, as c grows, bistability emerges and eventually disappears as only the high activation state is supported when c>cc (rightmost). A defining feature of bistability is the hysteresis effect, where the same value of a parameter may evoke different states depending on the history of activity. For example, the high activation state still exists for c less than the rightmost cc and can only be lost when c falls below the leftmost cc value. (ii) c is fixed while the negative regulation parameter r is varied. For small r, only the high activation state exists. As r grows larger, the system becomes bistable and, eventually, only the low state exists after crossing rc. Panel (iii) shows a parametric plot of the critical values cc(x) and rc(x), that partition the parameter space, and the bifurcation surface summarize the analysis completely (iv).

Original Research

22 November 2018

Analog Signaling With the “Digital” Molecular Switch CaMKII

Stephen E. Clarke

2,161 views

0 citations

Ventral tegmental area (VTA) but not substantia nigra pars compact (SNc) dopamine (DA) neurons express spike-timing-dependent (STD)-long-term depression (LTDGABA) in response to a complex spiking spike-timing-dependent plasticity (STDP) protocol. Panel (A) represents sample bursts of the complex spiking protocol for induction of LTDGABA. (B,C) Single and average experiments showing induction of STDP recorded in Ih(+) (presumably DA) neurons in VTA (filled square symbols) or SNc (filled circle symbols). At the arrow, STDP was induced. Insets: averaged inhibitory postsynaptic currents (IPSCs) before and 25 min after STDP protocol. In this and all figures, 10 consecutive traces from each condition were averaged for illustration as inset. Calibration: 100 pA, 25 ms (VTA: 75 ± 1.1% of pre-STDP values, F(3,22) = 7.5, p < 0.0001, n = 8; SNc: 103 ± 2.4% of pre-STDP values, F(5,70) = 1.26, n = 14). Values shown throughout figure are the mean ± SEM.

Brief Research Report

21 September 2018

Dopamine Receptor Activation Is Required for GABAergic Spike Timing-Dependent Plasticity in Response to Complex Spike Pairing in the Ventral Tegmental Area

Ludovic D. Langlois

, 1 more and

Fereshteh S. Nugent

3,666 views

3 citations

A visual depiction of (A) mechanistic calcium model and (B) the Input-Output spine calcium model. (A) portrays an interaction diagram of the mechanistic calcium model presented in the manuscript, with references the equations and kinetic schemas which govern the dynamics of each of the individual components. (B) In the IO model, the inputs and output correspond to parameters in the mechanistic model. Inputs to the IO model are NMDAr conductance and postsynaptic potential. Output is the estimate on calcium concentration in the spine. Coefficients are estimated based on the spine calcium mechanistic model, and presented in Supplementary Table 6.

Original Research

27 July 2018

A Glutamatergic Spine Model to Enable Multi-Scale Modeling of Nonlinear Calcium Dynamics

Eric Hu

, 4 more and

Theodore W. Berger

5,731 views

12 citations

Consequences on the release probability of calcium channel location and vesicular crowding at the AZ. Calcium time course in the pre-synaptic terminal and vesicular release activation. (A) Number of free (continuous) and buffered (dotted) ions for 0 (left), 100 (middle), and 400 (right) buffer sites. (B) Histogram of vesicular release time for the stochastic (blue), and the Markov-mass action model (red) for 0 (left), 100 (middle), and 400 (right) buffer sites.

Review

23 July 2018

The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release

Claire Guerrier

and

David Holcman

4,686 views

26 citations

Dopamine and acetylcholine shape spike-timing dependent plasticity (STDP) in hippocampus and prefrontal cortex. (A) Generic schematics of the main signaling pathways activated in STDP in response to dopamine, acetylcholine and glutamate. Full and tee-shaped arrows denote activation and inhibition, respectively. Gx, G-protein coupled receptor signaling x subclass; PKA, Protein kinase A, MEK-ERK (activation of MAPK); PP1, Protein Phosphatase-1; CaMKII, Ca2+/calmodulin-dependent protein kinase-II; DAG, diacylglycerol; PLC, phospholipase C. (B) In hippocampus, bidirectional Hebbian STDP observed in control conditions is converted to timing-dependent long-term potentiation (tLTP) when dopamine is applied during the STDP pairings or just after it. When dopamine is applied 10 and 30 min after STDP pairings, an absence of plasticity and timing-dependent long-term depression (tLTD) are observed, respectively. Adapted from Zhang et al. (2009) and Brzosko et al. (2015). Acetylcholine, applied during STDP pairings, converts bidirectional Hebbian STDP to unidirectional tLTD for both post-pre and pre-post pairings. Dopamine applied just after STDP pairings with acetylcholine during STDP pairings can rescue pre-post tLTP. Adapted from Brzosko et al. (2017). (C) In the prefrontal cortex, addition of dopamine or D1-plus D2-class receptor agonists to a pairing protocol that does not induce STDP promotes a unidirectional tLTP. The inhibition of GABAA receptors or application of agonists of D2-class receptors allows the expression of tLTP for pre-post pairings. Conversely, application of agonists of D1-class receptors allows the expression of tLTP for post-pre pairings. Activation of D2R expressed by gamma-aminobutyric acid (GABA)ergic interneurons (or their direct inhibition by GABAA receptor inhibitors) decreases activity of these interneurons uncovering tLTP for pre-post pairings. For post-pre pairings induction relies on D1-class receptor (located on the postsynaptic neuron) activation. Adapted from Xu and Yao (2010) and Ruan et al. (2014), with no permission required.

Review

03 July 2018

Modulation of Spike-Timing Dependent Plasticity: Towards the Inclusion of a Third Factor in Computational Models

Alexandre Foncelle

, 5 more and

Laurent Venance

14,940 views

56 citations

Review

16 May 2018

PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders

Brielle R. Ferguson

and

Wen-Jun Gao

Diagram shows how parvalbumin (PV) interneurons help maintain the excitation and inhibition (E/I) balance within prefrontal local circuits for optimal information processing and how they are modulated by subcortical inputs. Under normal conditions, PV interneurons are highly active to help maintain a high level of inhibition relative to excitation in pyramidal neurons (potentially mediated by MD inputs). This may help dampen the activity of neurons in functional units representing distracting information (left and right cortical columns), increasing the signal to noise of incoming task-related information from prefrontal cortex (PFC) afferents (listed on right). PV interneurons likely help regulate spike timing as well as oscillatory patterns, which in concert would increase the likelihood that neurons representing relevant information are active and can relay correct information to downstream structures, driving the proper execution of PFC-dependent behaviors.Vasoactive-intestinal peptide (VIP) interneurons may help further refine cortical representations by inhibiting somatostatin (SST) neurons that target distal dendrites to disinhibit groups of excitatory pyramidal neurons. Darker and lighter shaded neurons represent high vs. low levels of activity respectively. This model is modified from Ferguson and Gao (2018) and is based on data discussed in the text and known connectivity within and projections to the medial PFC (mPFC; Kuroda et al., 2004; Rotaru et al., 2005; Hoover and Vertes, 2007). Ongoing questions involve what subcortical structures provide the majority of excitatory input to each neuronal subtype to regulate their function, as well as the precise contribution of recurrent excitation in regulating inhibitory neurons to affect E/I balance. Note: Amyg, amygdala; BF, basal forebrain; DR, dorsal raphe; Hpc, hippocampus; LC, locus coeruleus; MD, mediodorsal thalamus; VTA, ventral tegmental area.

Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV) GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC) in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I) in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.

56,490 views

507 citations