scholarly journals Optogenetic activation of Gq signaling in astrocytes yields stimulation-specific effects on basal hippocampal synaptic excitation and inhibition

2021 ◽  
Author(s):  
Connor D Courtney ◽  
Courtney Sobieski ◽  
Charu Ramakrishnan ◽  
Robbie J Ingram ◽  
Natalia M Wojnowski ◽  
...  

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. Although there is growing evidence that astrocytes modulate synaptic excitation, the extent to which astrocytes modulate inhibition remains unknown. Additionally, tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we present AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), an astrocyte-specific viral vector that activates the Gq-mediated intracellular cascade via light-sensitive α1-adrenergic receptors. To determine if stimulation of Optoα1AR in astrocytes modulates hippocampal synaptic transmission, whole-cell recordings were made in CA1 pyramidal cells in slices with surrounding astrocytes expressing either Optoα1AR, channelrhodopsin (ChR2), or control green fluorescent protein (GFP). CA1 astrocytes were exposed to either low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s/intensity) or high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) blue light stimulation. Low-frequency stimulation of astrocytic Optoα1AR was insufficient to modulate the frequency or strength of either inhibitory or excitatory spontaneous postsynaptic currents (sIPSCs/sEPSCs), whereas the same stimulation of astrocytic ChR2 produced increases in sIPSC frequency and sEPSC frequency and amplitude. By contrast, 20 Hz stimulation of astrocytic Optoα1AR increased frequency of both miniature IPSCs and EPSCs, and the miniature IPSC frequency effect was largely reversible within 20 min after light stimulation. These data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission but only following high-frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.

2000 ◽  
Vol 83 (4) ◽  
pp. 2412-2420 ◽  
Author(s):  
Hiroshi Ikeda ◽  
Tatsuya Asai ◽  
Kazuyuki Murase

We investigated the neuronal plasticity in the spinal dorsal horn and its relationship with spinal inhibitory networks using an optical-imaging method that detects neuronal excitation. High-intensity single-pulse stimulation of the dorsal root activating both A and C fibers evoked an optical response in the lamina II (the substantia gelatinosa) of the dorsal horn in transverse slices of 12- to 25-day-old rat spinal cords stained with a voltage-sensitive dye, RH-482. The optical response, reflecting the net neuronal excitation along the slice-depth, was depressed by 28% for more than 1 h after a high-frequency conditioning stimulation of A fibers in the dorsal root (3 tetani of 100 Hz for 1 s with an interval of 10 s). The depression was not induced in a perfusion solution containing an NMDA antagonist,dl-2-amino-5-phosphonovaleric acid (AP5; 30 μM). In a solution containing the inhibitory amino acid antagonists bicuculline (1 μM) and strychnine (3 μM), and also in a low Cl−solution, the excitation evoked by the single-pulse stimulation was enhanced after the high-frequency stimulation by 31 and 18%, respectively. The enhanced response after conditioning was depotentiated by a low-frequency stimulation of A fibers (0.2–1 Hz for 10 min). Furthermore, once the low-frequency stimulation was applied, the high-frequency conditioning could not potentiate the excitation. Inhibitory transmissions thus regulate the mode of synaptic plasticity in the lamina II most likely at afferent terminals. The high-frequency conditioning elicits a long-term depression (LTD) of synaptic efficacy under a greater activity of inhibitory amino acids, but it results in a long-term potentiation (LTP) when inhibition is reduced. The low-frequency preconditioning inhibits the potentiation induction and maintenance by the high-frequency conditioning. These mechanisms might underlie robust changes of nociception, such as hypersensitivity after injury or inflammation and pain relief after electrical or cutaneous stimulation.


2021 ◽  
Vol 15 ◽  
Author(s):  
Carlos Silva ◽  
Blake S. Porter ◽  
Kristin L. Hillman

When performing tasks, animals must continually assess how much effort is being expended, and gage this against ever-changing physiological states. As effort costs mount, persisting in the task may be unwise. The anterior cingulate cortex (ACC) and the anterior insular cortex are implicated in this process of cost-benefit decision-making, yet their precise contributions toward driving effortful persistence are not well understood. Here we investigated whether electrical stimulation of the ACC or insular cortex would alter effortful persistence in a novel weightlifting task (WLT). In the WLT an animal is challenged to pull a rope 30 cm to trigger food reward dispensing. To make the action increasingly effortful, 45 g of weight is progressively added to the rope after every 10 successful pulls. The animal can quit the task at any point – with the rope weight at the time of quitting taken as the “break weight.” Ten male Sprague-Dawley rats were implanted with stimulating electrodes in either the ACC [cingulate cortex area 1 (Cg1) in rodent] or anterior insula and then assessed in the WLT during stimulation. Low-frequency (10 Hz), high-frequency (130 Hz), and sham stimulations were performed. We predicted that low-frequency stimulation (LFS) of Cg1 in particular would increase persistence in the WLT. Contrary to our predictions, LFS of Cg1 resulted in shorter session duration, lower break weights, and fewer attempts on the break weight. High-frequency stimulation of Cg1 led to an increase in time spent off-task. LFS of the anterior insula was associated with a marginal increase in attempts on the break weight. Taken together our data suggest that stimulation of the rodent Cg1 during an effortful task alters certain aspects of effortful behavior, while insula stimulation has little effect.


1991 ◽  
Vol 65 (6) ◽  
pp. 1313-1320 ◽  
Author(s):  
H. R. Koerber ◽  
L. M. Mendell

1. Monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in medial gastrocnemius motoneurons by maximal group Ia stimulation of the heteronymous lateral gastrocnemius-soleus nerve in anesthetized cats. Three different patterns of high-frequency stimulation were delivered to the nerve, and the EPSPs were averaged in register (1, 2, . . ., n) for each. 2. One pattern ("Burst") consisted of 32 shocks delivered every 2 s at an interstimulus interval of 6 ms (167 Hz). The second pattern ("Stepping") was a frequency-modulated burst of 52 shocks derived from a recording of a spindle during stepping and was delivered every 2 s. The third pattern ("Paw Shake") was from an extensor spindle afferent recorded during rapid paw shake and was delivered in groups of six bursts with an interburst interval of 75 ms and a 3-s pause between groups of six bursts. The EPSPs in each burst were averaged in register (1, 2, . . ., n) so that the relative amplitude of each EPSP in the burst could be ascertained. The EPSP produced by low-frequency stimulation of the nerve (18 Hz) was also recorded for each motoneuron. 3. The initial EPSP in most bursts was larger than the EPSP measured as a result of low-frequency stimulation. This potentiation, defined as the ratio of the amplitude of the initial EPSP of the response to that of the low-frequency control, was found to vary systematically as a function of amplitude of the control EPSP as well as the stimulus paradigm used.(ABSTRACT TRUNCATED AT 250 WORDS)


1990 ◽  
Vol 258 (5) ◽  
pp. H1334-H1338 ◽  
Author(s):  
A. Ohlen ◽  
M. G. Persson ◽  
L. Lindbom ◽  
L. E. Gustafsson ◽  
P. Hedqvist

Intravital microscopy was used to study the effect of motor nerve stimulation on microvessel diameters in the rabbit tenuissimus muscle. Stimulation of the motor nerve (0.5-5 ms, 2-20 Hz, 5-15 V) evoked pulse duration- and frequency-dependent constriction of transverse and terminal arterioles. The vasoconstriction induced by low-frequency stimulation (2 Hz) was abolished by the alpha-adrenoceptor antagonist phentolamine, whereas high-frequency stimulation (10-20 Hz) resulted in a response that was only partially inhibited by phentolamine. However, desensitization of the tissue to the vasoconstrictor effects of neuropeptide Y (NPY) changed the response remaining after phentolamine into vasodilatation. Independent of stimulation parameters, pretreatment of the tissue with the adrenergic neuron blocker guanethidine reversed the constriction into dilatation that was resistant to propranolol, atropine, and indomethacin. The results document the functional presence of both vasoconstrictor and vasodilator fibers in the rabbit tenuissimus muscle motor nerve, and they suggest that part of the nerve-induced vasoconstriction at higher stimulation frequencies is caused by neuronally released NPY.


2004 ◽  
Vol 92 (6) ◽  
pp. 3332-3337 ◽  
Author(s):  
Jens Ellrich

Long-term depression (LTD) of somatosensory processing has been demonstrated in slice preparations of the spinal dorsal horn. Although LTD could be reliably induced in vitro, inconsistent results were encountered when the same types of experiments were conducted in adult animals in vivo. We addressed the hypothesis that LTD of orofacial sensorimotor processing can be induced in mice under general anesthesia. The effects of electric low- and high-frequency conditioning stimulation of the tongue on the sensorimotor jaw-opening reflex (JOR) elicited by electric tongue stimulation were investigated. Low-frequency stimulation induced a sustained decrease of the reflex integral for ≥1 h after the end of conditioning stimulation. After additional high-frequency stimulation, the reflex partly recovered from LTD. High-frequency stimulation alone induced a transient increase of the JOR integral for <10 min. The LTD of the sensorimotor jaw-opening reflex in anesthetized mice may be an appropriate model to investigate the central mechanisms and the pharmacology of synaptic plasticity in the orofacial region. The application of electrophysiological techniques in mice provides the opportunity to include adequate knock-out models to elucidate the neurobiology of LTD.


1978 ◽  
Vol 74 (1) ◽  
pp. 101-113 ◽  
Author(s):  
EDWARD J. CATAPANE ◽  
GEORGE B. STEFANO ◽  
EDWARD AIELLO

The function of the CNS of Mytilus edulis was investigated for its role in the control of lateral ciliary activity. Ciliary beating rates were directly measured by stroboscopic microscopy of gill preparations which had the ipsilateral visceral ganglion (VG) attached. Low frequency electrical stimulation of the cerebrovisceral connective (CVC) or superfusion of the VG with serotonin increased lateral ciliary activity. This response could be antagonized by pretreating the gill with BOL or methysergide (MS), or by pretreating the VG with BOL, MS or ergonovine (ERG). High frequency stimulation of the CVC or superfusion of the VG with dopamine or epinephrine decreased lateral ciliary activity. This response could be antagonized by pretreating the gill with ERG or by pretreating the VG with ERG or MS. Acetylcholine and its mimetic acetylmethylcholine were found to be non-effective in altering ciliary activity in this study. The study demonstrates a reciprocal serotonergic-dopaminergic innervation of lateral gill ciliated cells originating in the CNS.


1965 ◽  
Vol 208 (5) ◽  
pp. 993-999 ◽  
Author(s):  
S. Katz ◽  
J. H. Perryman

Experiments on cats anesthetized with pentobarbital sodium indicate that a change in the frequency of peripheral nerve stimulation will alter the direction of the blood pressure and respiratory response only after a certain intensity of stimulation is attained. Low voltage-high frequency (1–3 v, 60/sec), high voltage-low frequency (15 v, 10/sec) and low voltage-low frequency stimulation of the tibial and/or peroneal nerves initially produces a decrease in blood pressure (20–50 mm Hg) and a decrease in respiratory minute volume (13–92%). However, high voltage-high frequency stimulation generally produces an increase in blood pressure of 10–65 mm Hg and an 8–14% increase in minute volume. In decerebrate cats, low-voltage, high-frequency as well as high-voltage, high-frequency stimulation of the tibial nerve results in an increase in blood pressure, minute volume, and/or rate and amplitude of phrenic nerve discharge. Frequency and intensity are therefore interrelated. Anatomical specificity of limb peripheral nerve fibers into pressor and depressor afferents is not substantiated.


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