What is the difference between phasic and tonic receptors

Phasic receptors adapt rapidly and inform, therefore, about the rate of change of a stimulus. Tonic receptors adapt slowly and inform about the presence and strength of a stimulus. Many sensory neurons may unify both response properties and are called phasic-tonic receptors. They usually show a phasic response at stimulus onset, followed by a long-lasting, but lower tonic response. Sensory Systems. Our skin includes touch and temperature receptors, and our inner ears contain sensory mechanoreceptors designed for detecting vibrations caused by sound or used to maintain balance.

Force -sensitive mechanoreceptors provide an example of how the placement of a sensory receptor plays a role in how our brains process sensory inputs. While the cutaneous touch receptors found in the dermis and epidermis of our skin and the muscle spindles that detect stretch in skeletal muscle are both mechanoreceptors, they serve discrete functions. In both cases, the mechanoreceptors detect physical forces that result from the movement of the local tissue, cutaneous touch receptors provide information to our brain about the external environment, while muscle spindle receptors provide information about our internal environment.

Muscle spindle : Mammalian muscle spindle showing typical position in a muscle left , neuronal connections in spinal cord middle , and an expanded schematic right. The spindle is a stretch receptor with its own motor supply consisting of several intrafusal muscle fibers. The sensory endings of a primary group Ia afferent and a secondary group II afferent coil around the non-contractile central portions of the intrafusal fibers.

Privacy Policy. Skip to main content. Peripheral Nervous System. Search for:. Sensory Receptors. Classification of Receptors by Stimulus Sensory receptors are primarily classified as chemoreceptors, thermoreceptors, mechanoreceptors, or photoreceptors. Learning Objectives Differentiate among the types of stimuli to which receptors respond.

Key Takeaways Key Points Chemoreceptors detect the presence of chemicals. Thermoreceptors detect changes in temperature. Mechanoreceptors detect mechanical forces.

This would be consistent with our results showing that the synaptic facilitation is favored and depression is reduced in mutant mice, in the absence of exogenous agonists. Thalamic reticular nucleus neurons innervate adjacent reticular neurons as well as VPM neurons and constitute the only inhibitory input in these two nuclei in mice Pinault and Deschenes, A Experimental configuration, including positions of electrical stimulation into the TRN and recording in adjacent reticular neurons.

In this context the contribution of endogenous glutamate release to activation of the receptor should be limited, suggesting that the mGlu7 receptor constitutively inhibits GABA release by TRN neurons. The above results showed that mGlu7a receptors control evoked synaptic activity in the thalamus. Here, we investigated whether the mGlu7a receptor could also affect the spontaneous synaptic activity of reticular neurons. Thalamic neurons relay sensory information to the barrel cortex, and VPM axon terminals project predominantly onto cortical layer 4, where three main classes of neurons are found: glutamatergic neurons i.

They are so-called on the basis of their firing pattern in response to current injection, as confirmed by our characterization Supplementary Figure 2. As thalamo-cortical and cortico-thalamic fibers follow the same path, we used an optogenetic approach to selectively stimulate thalamocortical afferents in brain slices Cruikshank et al. The mGlu7 receptor modulates glutamatergic transmission between VPM neurons and cortical layer 4 Fast-Spiking interneurons. A Experimental configuration and example of a thalamocortical slice expressing hChR2-mCherry in VPM thalamic neurons and their axons targeting cortical layer 4.

LED stimuli blue light, nm were directed on layer 4 thalamocortical hChR2-expressing terminals where postsynaptic responses of cortical neurons were recorded. Blue arrows indicate light stimulations. Please note the decrease in synaptic depression in the mGlu7 AAA mice. On the contrary, inhibition of single evoked EPSCs as well as synaptic depression ratio upon repetitive VPM afferent stimulations Figures 6H,I recorded from cortical layer 4 glutamatergic neurons and RS interneurons were similar in both mice genotypes.

Taken together, these results indicate an mGlu7a receptor PDZ dependent-pathway mediated inhibition of VPM glutamatergic contacts innervating cortical layer 4 FS interneurons, but not other studied cortical cell types. The lack of mGlu7-specific orthosteric antagonist prevented us to definitively conclude on whether mGlu7 has a constitutive, agonist-independent activity in acute TC slices.

Nevertheless we investigated whether the mGlu7 receptor NAM ADX displayed a true inverse agonist activity in the virtual absence of glutamate. Inverse agonists are a class of pharmacological compounds that block receptor constitutive activity. Importantly, co-transfection of the excitatory amino-acid transporter EAAC1 allowed lowering the extracellular glutamate concentration to a sub-micromolar range, unable to activate mGlu7a receptors P.

Rondard, IGF Montpellier, personal communication. We remarked a higher receptor activity as compared to the control transfection, which was increasingly proportional to the quantity of mGlu7a receptor expressed Figure 7A. This suggested a constitutive activity of the recombinant receptor. On the contrary, ADX inhibited basal IP1 production in the absence of agonist, likely resulting from constitutive activity of the recombinant mGlu7a receptor.

Constitutive activity of mGlu7a receptors in the absence of extracellular glutamate. Note that transfection of mGlu7a receptor in the absence of agonist induces IP1 synthesis. What is the physiological role of the mGlu7 receptor tonic activity?

CD-injected control mice continued normal exploratory activity and grooming, and showed no modification of their EEG pattern. The majority of WT mice 31 out of 36 mice injected with ADX showed a net decrease in exploratory activity and reactivity, entering a phase of prostration Figure 8A. The mGlu7a AAA mutant mice showed the typical absence-like behavior with repeated episodes of exploratory activity arrest and facial myoclonus previously reported Bertaso et al.

The scoring scale is given on the right. Traces in C,D show, respectively, SWD-like and low frequency activity with recurrent spikes corresponding to K-complexes. The level of wavelet power is represented using the color scale. In four cases out of 21, on top of the described sleep-related activity, we observed SWD with an intrinsic frequency of 8—10 Hz Figure 8C , similar to those spontaneously arising in non-treated mGlu7a AAA mice Figure 8E and Bertaso et al.

More details on frequency band analysis can be found in Supplementary Figure 3. These data show that pharmacological blockade of mGlu7 receptor tonic activity in vivo induces a lethargic state accompanied by abnormal sleep-related behavior and absence epileptic seizures. Despite its wide distribution and conservation among species Flor et al.

The homology with the other mGluRs has to date hindered the design of type-specific orthosteric agonists and antagonists. Here, we took advantage of the combination of a genetic mouse model and a new inverse agonist to challenge the classical view of mGlu7 as a receptor exclusively activated when glutamate concentration rises high. Our results show that mGlu7 receptors are functionally expressed at synapses formed onto and between TRN neurons, as well as VPM synapses onto fast-spiking interneurons of the somatosensory cortical layer 4.

Furthermore, we demonstrate the involvement of the mGlu7a receptor PDZ-dependent pathway in short-term plasticity enhancement, reinforcing depression, and reducing facilitation in WT mice. Previous work has shown that expression of the closely related mGlu4 receptor is not changed in the mGlu7a AAA mouse, nor is the localization of mGlu7 Zhang et al.

However, the results were not specific to the thalamocortical circuit. These data suggest that the receptor exerts a tonic modulation of basal synaptic transmission by constantly and specifically shaping low frequency excitatory and inhibitory postsynaptic responses. This novel mode of action of the receptor takes place in near-physiological conditions, in addition to its classical low-pass filter action during enhanced synaptic activity.

The receptor modulates both GABAergic and glutamatergic transmission in the thalamus, and its inhibition has consequences on animal behavior. Our work indicates that endogenous WT mGlu7 receptors are tonically active. Due to the limitations brought by the available pharmacology we cannot exclude a contribution of elicited glutamate release to the activity of the receptor.

However, we may deduce that at least part of the effect was due to an agonist-independent activity. Several arguments favor the existence of a constitutive activity of mGlu7.

First, our results in HEK cells show that, in an isolated system where the receptor expression and glutamate concentration are tightly controlled, mGlu7 receptors can act in an agonist-independent manner. We previously proposed the existence of a tonic mGlu7a receptor-mediated inhibition of voltage-gated calcium channels in cultured cerebellar granule cells, antagonized by binding of the protein kinase C substrate MacMARCKS to the receptor C-terminal tail Bertaso et al.

Recent data in dissociated superior cervical ganglia neurons showed that transfection of mGlu7a receptor is sufficient to induce spontaneous receptor intracellular signaling, and to inhibit voltage-dependent calcium channels Kammermeier, However, the inverse agonist used in the study, MMPIP, seems to have a different effect depending on the cellular context Niswender et al.

The future discovery of a true, mGlu7-specific negative orthosteric antagonist will allow to confirm these results in a clear-cut way. What could be the physiological role of the mGlu7a receptor PDZ-dependent tonic activity? Genetic mouse models allowed a deeper understanding of the mGlu7 receptor synaptic functions. We found that in the TC network, mGlu7a receptor-expressing synapses display higher short-term synaptic depression than mGlu7a AAA mutant synapses.

Pelkey et al. The PDZ interaction of mGlu7a with PICK1 is required for the receptor intracellular signaling, which could explain these effects, but whether or not control of the receptor tonic activity by PDZ interaction is required remains open. A tentative hypothesis is that such a tonic modulation of synaptic activities probably results from tonic activity of mGlu7 receptors.

This may have the following consequences on the TC network functions summarized in Figure 9 :. Summary of findings on functional expression of mGlu7 receptors in the thalamocortical network and alterations brought by the loss of mGlu7 constitutive activity or by the mGlu7a AAA mutation. This effect is amplified by the reticular neurons-mediated spontaneous phasic and tonic hyper-inhibition of thalamic cells.

Interestingly, increased TRN neurons-mediated tonic inhibition has been observed in all the other absence epilepsy models Cope and Di Giovanni, Hyperpolarization of VPM neurons is able to switch their firing pattern from tonic to burst mode, typically observed during absence seizures Huguenard and McCormick, This would be more likely in mGlu7a AAA as opposed to WT mice, where tonic activity of mGlu7 would provide a permanent control of those bursts. This effect mediated by mGlu7a receptor PDZ interaction should therefore prevent synchronization of the TRN neurons and protect against absence seizures.

Intra-TRN connections are known to slowly disappear during cerebral maturation in mice Pinault, Therefore this protective effect would be lost in adult mice, which may support the difference in the age at which absence seizures appear in rodent models compared to human Crunelli and Leresche, Similarly, Errington et al. Given the low affinity of the receptor for glutamate, it is possible that in physiological conditions the mGlu7 receptor acts mainly via its tonic rather than phasic agonist-dependent activity, at least at GABAergic synapses where the concentration of glutamate is expected to be low.

All these data highlight the fact that the physiological function of the mGlu7 receptor seems of particular importance to modulate inputs onto GABAergic neurons. The phenotypic abnormalities found in mGlu7 receptor mutant models reflect the strength of these synaptic controls in WT CNS. It is also interesting to underline the emerging concept that mGlu7 is capable to inhibit synaptic transmission in a target-specific manner, as shown by the differential effect on synapses harboring from VPM neurons to either the cortical layer 4 excitatory neurons no effect of mGlu7 or FS interneurons inhibition.

Interestingly, synapse-specific expression of mGlu7 has been found in hippocampal CA1 synapses onto interneurons expressing a postsynaptic protein, Elfn1 Tomioka et al. Recently, Klar et al. Incidentally, the lack of mGlu7-dependent inhibition observed in the VPM is in agreement with previous immunohistochemical data showing the absence of mGlu7 receptor in mouse VPM Kinoshita et al. This could reflect a variety of mechanisms. These effects might deplete the releasable pool of neurotransmitter in presynaptic sites, leading to a synaptic depression.

Alternative explanations could be the internalization of postsynaptic receptors after sustained neurotransmitter release or a decrease in thalamic fiber excitability. A few studies have highlighted the link of mGlu receptors with absence seizures Snead and Banerjee, ; Bertaso et al.

In vivo administration of ADX enhanced thalamic oscillations in association with drowsiness and behavioral arrest in WT mice. In vitro activation of mGlu7 by L-AP4 in rats reduces spindle oscillations, which typically occur during the early stage of sleep or during active phases of slow-wave-sleep oscillations Kyuyoung and Huguenard, As both sleep and absence seizures are supported by reciprocal connections between glutamatergic VPM and GABAergic TRN neurons, and somatosensory cortex Steriade, ; Huguenard and McCormick, , our data suggest that tonic activity of the mGlu7 receptor prevents unbalanced activity of the network that would lead to abnormal sleep-related behavior or seizures.

The border between the lethargic effect and absence seizures seems blurry, as in a few animals the EEG revealed SWDs typical of epileptic seizures. Alternatively, one could imagine an occlusion mechanism between the mutation of the receptor PDZ ligand motif and the action of ADX Overall, it appears that the mGlu7 receptor modulates the global thalamic state of excitability, reducing its propensity to switch from the tonic to the oscillatory mode.

In human, GRM7 gene polymorphisms have recently been associated with autism Yang and Pan, , schizophrenia Ohtsuki et al. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Deisseroth for the hChR2-mCherry construct, H. Adesnik, M. Bagnall, L. Ceolin, S. Dadak, F. De Bock, R.

Lambert, and J. Ster for useful discussion. Ango, F. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature , — Beenhakker, M.

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