Short-term plasticity

…through a basic mechanism known as short-term plasticity (STP). However, these synaptic dynamics exhibit considerable heterogeneity both within and across genetically defined cell types which poses a critical barrier to interpreting this language. Beninger et al. addressed this heterogeneity in excitatory human and rodent synapses by organizing their dynamics into functional subtypes which cannot be explained by continuum hypotheses and partly overl

…WM might partly be explained by short-term plasticity (STP) [7], where perceptual encoding leaves a neural trace that can be retrieved using perturbation methods [8,9]. However, STP traces cannot easily withstand continual visual stimulation. In contrast, $modulatory$ top-down feedback [10] (i.e., altering spiking propensity without inducing spiking directly [11]) from frontal regions to EVC

…plausible synaptic and neural plasticity mechanisms have been proposed. We show that these proposed short-term plasticity mechanisms may not necessarily be competing explanations, but instead yield interesting functional interactions on a wide set of WM tasks and enhance the biological plausibility of spiking neural network models of WM. While reductionist models (WM explained by one particular mechanism) are theoretically appealing and have increased our understanding of specific mechanisms, they are insufficient. WM mo

Besides its role in triggering fast neurotransmitter release, the protein Synaptotagmin-1 (Syt1) is also involved in the docking and priming process of synaptic vesicles (SVs) to the presynaptic active zone. Research indicates that Synaptotagmin-7 (Syt7) shares some functions with Syt1, but the specific mechanisms by which Syt7 exerts these functions are not well understood. To investigate the putative redundant role of Syt1/Syt7 in SV docking and priming we performed various experiments as high-pressure freezing and electron microscopy on hippocampal cultures, and electrophysiological recordi

Stress during adolescence is a known risk factor for neuropsychiatric disorders later in life, but how different factors alter the susceptibility to lasting cognitive or affective impairment is only partially understood. Here, we asked whether activin, a member of the TGF-β family, has a role in this process, the rationale being that activin affects the neural underpinnings of cognitive performance and affective behavior in the adult brain. We combined a mouse model of adolescent stress (corticosterone between postnatal days 30-45) with a transgenic mouse line expressing a dominant-negative mu

The entopeduncular nucleus EP, one of the basal ganglia(BGs), is considered one of the essential output nuclei, sending synapses belonging to the pathways essential for normal motor activity to two specific regions in the ventral lateral thalamic nuclei(VL) and ventral anterior thalamic nuclei(VA).The basal ganglia innervate the thalamus through 3 pathways:direct, indirect, and hyper-direct.By these three pathways, we get an innervation that causes disinhibition or inhibition of the thalamus.The research aimed to study the thalamus, the relay center for transmitting information received from m

ALS is the most common motor neuron disease in humans, whereby upper and lower motor neurons degenerate. A major hypothesis underlying the mechanistic origin of neurodegeneration in ALS postulates that cortical hyperexcitability facilitates cell death. Previous research has identified the G4C2 hexanucleotide repeat expansion in the C9orf72 gene as the most common genetic cause of ALS; however, little is known about the contribution of the C9orf72 gene to neuronal excitability and synaptic dysfunction in the primary motor cortex. Thus, using C9orf72 knockout loss-of-function (C9-KO LOF) and gai

…role of APP in presynaptic plasticity and information transfer within the hippocampus. We deleted APP and the related protein APLP2 in dentate gyrus granular cells (GCs) using a viral gene transfer strat

Fragile X syndrome is the most common form of inherited intellectual disability and a major cause of autism spectrum disorder. This syndrome is caused by the silencing of the Fmr1 gene, which codes for the RNA-binding protein, FMRP. Most studies have focused on dendritic and postsynaptic mechanisms. Here we aim at characterising the functional involvement of new FMRP targets by exploring the consequences of FMRP loss on presynaptic mechanisms. We focus in particular on a recently identified target, Phosphodiesterase 2A (PDE2A). PDE2A is located in the presynaptic compartment and is highly expr

The Cerebellar Nuclei (CN) are the sole output of the cerebellum, integrating and relaying information computed in the cerebellar cortex and transmitted by Purkinje cells, before sending it to the downstream targets of the cerebellum. The cerebellum receives two types of afferents: mossy fibers (sensory-motor context) and climbing fibers (teaching signals). These inputs project to the cerebellar cortex, with some also sending direct excitatory collaterals to the CN. However, little is known about the functional properties and the impact of these excitatory inputs on the firing of cerebellar nu

Short-term plasticity (STP) is the neuronal substrate for modification of the efficiency of synaptic transmission in the timescale of milliseconds to seconds. STP renders synapses the ability to process and integrate inputs which in-turn controls information flow and processing in networks. Our work explored the diversity in STP of hippocampal CA1 synapses and the summation of multiple inputs during STP in a CA1 neuron with balanced excitation and inhibition. We performed invitro experiments on the CA3-CA1 network in acute hippocampal slices from mice expressing channelrhodopsin specifically i

The hippocampal CA3-CA1 circuit is critical for memory encoding and retrieval. Previous work has shown this feedforward excitatory-inhibitory network (FFEI) maintains a precise excitation-inhibition (E-I) balance onto CA1 pyramidal cells (CA1PCs) (Bhatia et al, 2019). However, how this balance dynamically evolves dependent of the history of sustained input activity is unclear. Deviations from E-I balance are important for gating, normalization, and representation of input ensembles. Using in vitro whole-cell recordings in mouse hippocampal slices, we probed E-I balance by optogenetically evok

The cerebellum is an area of the brain involved in sensory-motor adaptation, movement coordination and higher cognitive processes. Within the cerebellar cortex, mossy fibres (MFs) convey sensorimotor input to a dense layer of granule cells (GrCs). GrCs relay this information through parallel fibre (PF) projections that synapse with Purkinje cells (PCs), the sole output of the cerebellar cortex, and molecular layer interneurons (MLI), which provide feedforward inhibition of PCs. Accordingly, PCs compute incoming sensorimotor patterns and send inhibitory outputs that rapidly adjust motor movemen

In nature, diverse sensory signals fluctuate in time and in space. Odors, for example, are distorted by wind into narrow filaments. When multiple spatially distinct odor sources exist, these filaments interleave but do not intermix. Such odor landscapes pose complementary challenges to animals – such as the fruit fly – that depend on olfaction to find food or mating partners. First, to select the best odor to track back to its source, the olfactory system must compare information from different filaments over relatively long timescales. Second, to remain on high alert to unexpected changes, su

Human invasive EEG recordings are used to guide clinical decision-making for epilepsy patients and offer an opportunity to better understand underlying neurophysiology. However, the relationship between macroscale electrophysiological recordings and underlying neural networks mechanisms remain unclear. Lundstrom et al [1,2] have shown that interictal (between-seizure) low frequency EEG activity (<1 Hz) is decreased at the seizure onset zone (SOZ), while higher frequency activity (1-50 Hz) is increased. These changes result in interictal power spectral densities (PSDs) with flattened slopes

One elementary brain function that underlies many of our cognitive behaviors is the ability to maintain parametric information briefly in mind, in the time scale of seconds, to span delays between sensory information and actions. This component of working memory is fragile and quickly degrades with delay length. Under the assumption that behavioral delay-dependencies mark core functions of the working memory system, our goal is to find a neural circuit model that represents their neural mechanisms and apply it to research on working memory deficits in neuropsychiatric disorders. We have constr

Inhibitory neurons in the cortex are highly diverse in terms of anatomy, electrophysiology and functions. In the mouse cortex, three major classes of interneurons expressing parvalbumin (PV), somatostatin (SST) and vasoactive intestinal peptide (VIP) constitute more than 80% of GABAergic interneurons. Together with excitatory (E) neurons, they form a canonical microcircuit relevant for cortical computations. Multiple experimental studies have revealed that this canonical microcircuit can exhibit counterintuitive nonlinear behavior. More specifically, the circuit can perform response reversal w

Distress calls of mice pups outside their nest elicit reliable pup retrieval in maternal female mice but not in their virgin (`naive') conspecifics. However, when co-housed with maternal mice, naive mice become `experienced' and learn to reliably perform pup retrieval. This process correlates with neuronal changes in the primary auditory cortex (A1): While excitatory (E) neuron responses are sharply tuned to a certain inter- pup-call interval and inhibitory (I) neuron responses are broadly tuned in naive mice, the two neuron types are co-tuned in experienced mice. This change in behavior and t

Cortical circuits process information by rich recurrent interactions between excitatory neurons and inhibitory interneurons. One of the prime functions of interneurons is to stabilize the circuit by feedback inhibition, but the level of specificity on which inhibitory feedback operates is not fully resolved. We hypothesized that inhibitory circuits could enable separate feedback control loops for different synaptic input streams, by means of specific feedback inhibition to different neuronal compartments. To investigate this hypothesis, we adopted an optimization approach. Leveraging recent ad

…that directly affects long-term plasticity (LTP) (the cellular underpinning of memory). It is therefore considered a critical regulator of learning and memory in the brain. Its action via M4 metabotropic receptors in the presynaptic terminal of the CA3 neurons and M1 metabotropic receptors in the postsynaptic spines of CA1 neurons produce rich dynamics across multiple timescales. We developed a model