Short-Term Plasticity at Inhibitory Synapses in Rat Striatum and Its Effects on Striatal Output

2001 ◽  
Vol 85 (5) ◽  
pp. 2088-2099 ◽  
Author(s):  
John S. Fitzpatrick ◽  
Garnik Akopian ◽  
John P. Walsh

Two forms of short-term plasticity at inhibitory synapses were investigated in adult rat striatal brain slices using intracellular recordings. Intrastriatal stimulation in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM) andd,l-2-amino-5-phosphonovaleric acid (50 μM) produced an inhibitory postsynaptic potential (IPSP) that reversed polarity at −76 ± 1 (SE) mV and was sensitive to bicuculline (30 μM). The IPSP rectified at hyperpolarized membrane potentials due in part to activation of K+ channels. The IPSP exhibited two forms of short-term plasticity, paired-pulse depression (PPD) and synaptic augmentation. PPD lasted for several seconds and was greatest at interstimulus intervals (ISIs) of several hundred milliseconds, reducing the IPSP to 80 ± 2% of its control amplitude at an ISI of 200 ms. Augmentation of the IPSP, elicited by a conditioning train of 15 stimuli applied at 20 Hz, was 119 ± 1% of control when sampled 2 s after the conditioning train. Augmentation decayed with a time constant of 10 s. We tested if PPD and augmentation modify the ability of the IPSP to prevent the generation of action potentials. A train of action potentials triggered by a depolarizing current injection of constant amplitude could be interrupted by stimulation of an IPSP. If this IPSP was the second in a pair of IPSPs, it was less effective in blocking spikes due to PPD. By contrast, augmented IPSPs were more effective in blocking spikes. The same results were achieved when action potentials were triggered by a depolarizing current injection of varying amplitude, a manipulation that produces nearly identical spike times from trial to trial and approximates the in vivo behavior of these neurons. These results demonstrate that short-term plasticity of inhibition can modify the output of the striatum and thus may be an important component of information processing during behaviors that involve the striatum.

2022 ◽  
Author(s):  
Lester Torres Cadenas ◽  
Hui Cheng ◽  
Catherine J.C. Weisz

The descending auditory system modulates the ascending system at every level. The final descending, or efferent stage, is comprised of lateral olivocochlear (LOC) and medial olivocochlear (MOC) neurons. MOC somata in the ventral brainstem project axons to the cochlea to synapse onto outer hair cells (OHC), inhibiting OHC-mediated cochlear amplification. MOC suppression of OHC function is implicated in cochlear gain control with changing sound intensity, detection of salient stimuli, attention, and protection against acoustic trauma. Thus, sound excites MOC neurons to provide negative feedback of the cochlea. Sound also inhibits MOC neurons via medial nucleus of the trapezoid body (MNTB) neurons. However, MNTB-MOC synapses exhibit short-term depression, suggesting reduced MNTB-MOC inhibition during sustained stimuli. Further, due to high rates of both baseline and sound-evoked activity in MNTB neurons in vivo, MNTB-MOC synapses may be tonically depressed. To probe this, we characterized short-term plasticity of MNTB-MOC synapses in mouse brain slices. We mimicked in vivo-like temperature and extracellular calcium conditions, and in vivo-like activity patterns of fast synaptic activation rates, sustained activation, and prior tonic activity. Synaptic depression was sensitive to extracellular calcium concentration and temperature. During rapid MNTB axon stimulation, post-synaptic currents (PSCs) in MOC neurons summated but with concurrent depression, resulting in smaller, sustained currents, suggesting tonic inhibition of MOC neurons during rapid circuit activity. Low levels of baseline MNTB activity did not significantly reduce responses to subsequent rapid activity that mimics sound stimulation, indicating that, in vivo, MNTB inhibition of MOC neurons persists despite tonic synaptic depression.


2006 ◽  
Vol 95 (2) ◽  
pp. 1285-1290 ◽  
Author(s):  
Enrico Bracci ◽  
Stefano Panzeri

The ability of synaptically released GABA to facilitate action potential generation in striatal projection neurons was studied in brain slices using current-clamp, gramicidin-perforated whole cell recordings. Evoked GABAergic postsynaptic potentials (PSPs) were pharmacologically isolated with ionotropic glutamate receptor antagonists. Subthreshold depolarizing current injections were paired with GABAergic PSPs at different intervals. GABAergic PSPs were able to convert current injection-induced depolarizations from subthreshold to suprathreshold, but only when they preceded the current injection by an appropriate interval; accordingly, action potentials were observed 4–140 ms after the onset of the GABAergic PSP, and their likelihood was maximal after 50–60 ms. The GABAergic excitatory effects were fully blocked by the GABAA receptor antagonist bicuculline. Appropriately timed GABA PSPs decreased the time taken by current injections to depolarize projection neurons, causing an apparent reduction in the spike threshold. In control solution, the ability of evoked PSPs (comprising both glutamatergic and GABAergic components) to reach spike threshold was often impaired by bicuculline. We conclude that GABAergic PSPs can exert excitatory effects on projection neurons and that this ability crucially depends on the timing between the GABAergic event and a concomitant depolarizing input.


2020 ◽  
Vol 123 (3) ◽  
pp. 1120-1132 ◽  
Author(s):  
Fu-Wen Zhou ◽  
Zuo-Yi Shao ◽  
Michael T. Shipley ◽  
Adam C. Puche

Short-term plasticity is a fundamental synaptic property thought to underlie memory and neural processing. The glomerular microcircuit comprises complex excitatory and inhibitory interactions and transmits olfactory nerve signals to the excitatory output neurons, mitral/tufted cells (M/TCs). The major glomerular inhibitory interneurons, short axon cells (SACs) and periglomerular cells (PGCs), both provide feedforward and feedback inhibition to M/TCs and have reciprocal inhibitory synapses between each other. Olfactory input is episodically driven by sniffing. We hypothesized that frequency-dependent short-term plasticity within these inhibitory circuits could influence signals sent to higher-order olfactory networks. To assess short-term plasticity in glomerular circuits and MC outputs, we virally delivered channelrhodopsin-2 (ChR2) in glutamic acid decarboxylase-65 promotor (GAD2-cre) or tyrosine hydroxylase promoter (TH-cre) mice and selectively activated one of these two populations while recording from cells of the other population or from MCs. Selective activation of TH-ChR2-expressing SACs inhibited all recorded GAD2-green fluorescent protein(GFP)-expressing presumptive PGC cells, and activation of GAD2-ChR2 cells inhibited TH-GFP-expressing SACs, indicating reciprocal inhibitory connections. SAC synaptic inhibition of GAD2-expressing cells was significantly facilitated at 5–10 Hz activation frequencies. In contrast, GAD2-ChR2 cell inhibition of TH-expressing cells was activation-frequency independent. Both SAC and PGC inhibition of MCs also exhibited short-term plasticity, pronounced in the 5–20 Hz range corresponding to investigative sniffing frequency ranges. In paired SAC and olfactory nerve electrical stimulations, the SAC to MC synapse was able to markedly suppress MC spiking. These data suggest that short-term plasticity across investigative sniffing ranges may differentially regulate intra- and interglomerular inhibitory circuits to dynamically shape glomerular output signals to downstream targets. NEW & NOTEWORTHY Short-term plasticity is a fundamental synaptic property that modulates synaptic strength based on preceding activity of the synapse. In rodent olfaction, sensory input arrives episodically driven by sniffing rates ranging from quiescent respiration (1–2 Hz) through to investigative sniffing (5–10 Hz). Here we show that glomerular inhibitory networks are exquisitely sensitive to input frequencies and exhibit plasticity proportional to investigative sniffing frequencies. This indicates that olfactory glomerular circuits are dynamically modulated by episodic sniffing input.


1996 ◽  
Vol 5 (6) ◽  
pp. 599-611 ◽  
Author(s):  
Rosemary A. Fricker ◽  
Roger A. Barker ◽  
James W. Fawcett ◽  
Stephen B. Dunnett

Cell suspension grafts from embryonic striatal primordia placed into the adult rat striatum survive well and are able to alleviate a number of behavioral deficits caused by excitotoxic lesions to this structure. However, neither the anatomical connectivity between the graft and host nor the functional recovery elicited by the grafts is completely restored. One way in which the survival and function of embryonic striatal grafts may be enhanced is by the improvement of techniques for the preparation of the cell suspension prior to implantation, an issue that has been addressed only to a limited extent. We have evaluated a number of parameters during the preparation procedure, looking at the effects on cell survival over the first 24 h from preparation using vital dyes and the numbers of surviving neurons in vitro, after 4 days in culture, in addition to graft survival and function in vivo. Factors influencing cell survival include the type of trypsinization procedure and the age of donor tissues used for suspension preparation. The presence of DNase has no effect on cell viability but aids the dissociation of the tissue to form single cells. These results have important implications for the use of embryonic striatal grafts in animal models of Huntington's disease, and in any future clinical application of this research.


2015 ◽  
Vol 113 (2) ◽  
pp. 509-523 ◽  
Author(s):  
Vishwa Goudar ◽  
Dean V. Buonomano

Determining the order of sensory events separated by a few hundred milliseconds is critical to many forms of sensory processing, including vocalization and speech discrimination. Although many experimental studies have recorded from auditory order-sensitive and order-selective neurons, the underlying mechanisms are poorly understood. Here we demonstrate that universal properties of cortical synapses—short-term synaptic plasticity of excitatory and inhibitory synapses—are well suited for the generation of order-selective neural responses. Using computational models of canonical disynaptic circuits, we show that the dynamic changes in the balance of excitation and inhibition imposed by short-term plasticity lead to the generation of order-selective responses. Parametric analyses predict that among the forms of short-term plasticity expressed at excitatory-to-excitatory, excitatory-to-inhibitory, and inhibitory-to-excitatory synapses, the single most important contributor to order-selectivity is the paired-pulse depression of inhibitory postsynaptic potentials (IPSPs). A topographic model of the auditory cortex that incorporates short-term plasticity accounts for both context-dependent suppression and enhancement in response to paired tones. Together these results provide a framework to account for an important computational problem based on ubiquitous synaptic properties that did not yet have a clearly established computational function. Additionally, these studies suggest that disynaptic circuits represent a fundamental computational unit that is capable of processing both spatial and temporal information.


Endocrinology ◽  
2010 ◽  
Vol 151 (6) ◽  
pp. 2911-2922 ◽  
Author(s):  
Mark J. McCabe ◽  
Gerard A. Tarulli ◽  
Sarah J. Meachem ◽  
David M. Robertson ◽  
Peter M. Smooker ◽  
...  

Sertoli cell tight junctions (TJs) are an essential component of the blood-testis barrier required for spermatogenesis; however, the role of gonadotropins in their maintenance is unknown. This study aimed to investigate the effect of gonadotropin suppression and short-term replacement on TJ function and TJ protein (occludin and claudin-11) expression and localization, in an adult rat model in vivo. Rats (n = 10/group) received the GnRH antagonist, acyline, for 7 wk to suppress gonadotropins. Three groups then received for 7 d: 1) human recombinant FSH, 2) human chorionic gonadotropin (hCG) and rat FSH antibody (to study testicular androgen stimulation alone), and 3) hCG alone (to study testicular androgen and pituitary FSH production). TJ proteins were assessed by real-time PCR, Western blot analysis, and immunohistochemistry, whereas TJ function was assessed with a biotin permeation tracer. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids). In contrast to controls, acyline induced seminiferous tubule permeability to biotin, loss of tubule lumens, and loss of occludin, but redistribution of claudin-11, immunostaining. Short-term hormone replacement stimulated significant recoveries in adluminal germ cell numbers. In hCG ± FSH antibody-treated rats, occludin and claudin-11 protein relocalized at the TJ, but such relocalization was minimal with FSH alone. Tubule lumens also reappeared, but most tubules remained permeable to biotin tracer, despite the presence of occludin. It is concluded that gonadotropins maintain Sertoli cell TJs in the adult rat via a mechanism that includes the localization of occludin and claudin-11 at functional TJs.


2007 ◽  
Vol 97 (4) ◽  
pp. 2863-2874 ◽  
Author(s):  
K. M. MacLeod ◽  
T. K. Horiuchi ◽  
C. E. Carr

The nature of the synaptic connection from the auditory nerve onto the cochlear nucleus neurons has a profound impact on how sound information is transmitted. Short-term synaptic plasticity, by dynamically modulating synaptic strength, filters information contained in the firing patterns. In the sound-localization circuits of the brain stem, the synapses of the timing pathway are characterized by strong short-term depression. We investigated the short-term synaptic plasticity of the inputs to the bird's cochlear nucleus angularis (NA), which encodes intensity information, by using chick embryonic brain slices and trains of electrical stimulation. These excitatory inputs expressed a mixture of short-term facilitation and depression, unlike those in the timing nuclei that only depressed. Facilitation and depression at NA synapses were balanced such that postsynaptic response amplitude was often maintained throughout the train at high firing rates (>100 Hz). The steady-state input rate relationship of the balanced synapses linearly conveyed rate information and therefore transmits intensity information encoded as a rate code in the nerve. A quantitative model of synaptic transmission could account for the plasticity by including facilitation of release (with a time constant of ∼40 ms), and a two-step recovery from depression (with one slow time constant of ∼8 s, and one fast time constant of ∼20 ms). A simulation using the model fit to NA synapses and auditory nerve spike trains from recordings in vivo confirmed that these synapses can convey intensity information contained in natural train inputs.


1995 ◽  
Vol 13 (7) ◽  
pp. 695-704 ◽  
Author(s):  
Jerzy W. Łazarewicz ◽  
Małgorzata Puka-Sundvall ◽  
Roman Gadamski ◽  
Mats Sandberg ◽  
Henrik Hagberg

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Mark D. Condon ◽  
Nicola J. Platt ◽  
Yan-Feng Zhang ◽  
Bradley M. Roberts ◽  
Michael A. Clements ◽  
...  

Abstract Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing release probability and axonal activity in determining short‐term plasticity of dopamine release, using fast‐scan cyclic voltammetry in the ex vivo mouse striatum. We show that brief short‐term facilitation and longer short term depression are only weakly dependent on the level of initial release, i.e. are release insensitive. Rather, short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+‐gated excitability and the dopamine transporter, particularly in the dorsal striatum. We identify the dopamine transporter as a master regulator of dopamine short‐term plasticity, governing the balance between release‐dependent and independent mechanisms that also show region‐specific gating.


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