scholarly journals Vasoactive Intestinal Peptide Selectively Depolarizes Thalamic Relay Neurons and Attenuates Intrathalamic Rhythmic Activity

2003 ◽  
Vol 90 (2) ◽  
pp. 1224-1234 ◽  
Author(s):  
Sang-Hun Lee ◽  
Charles L. Cox
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Information Transfer ◽  
Slow Wave Sleep ◽  
Rhythmic Activity ◽  
Absence Epilepsy ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Unit Recording ◽  
Recording Techniques ◽  
Relay Neurons

The reciprocal synaptic relationship between the relay thalamus and surrounding thalamic reticular nucleus can lead to the generation of various rhythmic activities that are associated with different levels of behavioral states as well as certain pathophysiological conditions. Intrathalamic rhythmic activities may be attenuated by numerous neuromodulators that arise from a variety of brain stem nuclei. This study focuses on the potential role of a particular neuropeptide, vasoactive intestinal peptide (VIP). VIP and its receptors are localized within the thalamic circuit and thus may serve as an endogenous modulator of the rhythmic activity. Using extracellular multiple-unit recording techniques, we found that VIP strongly attenuated the slow, 2- to 4-Hz intrathalamic rhythm. This rhythm is similar to that observed during slow wave sleep and certain pathophysiological conditions such as generalized absence epilepsy. Using intracellular recording techniques, we found that VIP selectively depolarized relay neurons in the ventrobasal nucleus but had negligible actions on neurons in thalamic reticular nucleus. The VIP-mediated depolarization is produced via an enhancement of the nonselective cation conductance, Ih. The antioscillatory actions of VIP likely occur by shifting the membrane potential to decrease the probability of burst discharge by relay neurons, a requirement to maintain the rhythmic activity. Not only does VIP alter the intrathalamic rhythmic activity, this peptide that is endogenous to the thalamic circuit may also play a significant role in the regulation of information transfer through the thalamocortical circuit.

Excitatory Actions of Vasoactive Intestinal Peptide on Mouse Thalamocortical Neurons Are Mediated by VPAC2 Receptors

2006 ◽  
Vol 96 (2) ◽  
pp. 858-871 ◽  
Author(s):  
Sang-Hun Lee ◽  
Charles L. Cox
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Information Transfer ◽  
Receptor Activation ◽  
Absence Epilepsy ◽  
Minor Role ◽  
Receptor Subtype ◽  
Thalamic Nuclei ◽  
Knock Out ◽  
A Minor ◽  
Relay Neurons

Thalamic nuclei can generate intrathalamic rhythms similar to those observed at various arousal levels and pathophysiological conditions such as absence epilepsy. These rhythmic activities can be altered by a variety of neuromodulators that arise from brain stem regions as well as those that are intrinsic to the thalamic circuitry. Vasoactive intestinal peptide (VIP) is a neuropeptide localized within the thalamus and strongly attenuates intrathalamic rhythms via an unidentified receptor subtype. We have used transgenic mice lacking a specific VIP receptor, VPAC2, to identify its role in VIP-mediated actions in the thalamus. VIP strongly attenuated both the slow, 2–4 Hz and spindle-like 5–8 Hz rhythmic activities in slices from wild-type mice (VPAC2+/+) but not in slices from VPAC2 receptor knock-out mice (VPAC2−/−), which suggests a major role of VPAC2 receptors in the antioscillatory actions of VIP. Intracellular recordings revealed that VIP depolarized all relay neurons tested from VPAC2+/+ mice. In VPAC2−/− mice, however, VIP produced no membrane depolarization in 80% of neurons tested. In relay neurons from VPAC2+/+ mice, VIP enhanced the hyperpolarization-activated mixed cation current, Ih, via cyclic AMP activity, but VIP did not alter Ih in VPAC2−/− mice. In VPAC2−/− mice, pituitary adenylate cyclase activating-polypeptide (PACAP) depolarized the majority of relay neurons via Ih enhancement presumably via PAC1 receptor activation. Our findings suggest that VIP-mediated actions are predominantly mediated by VPAC2 receptors, but PAC1 receptors may play a minor role. The excitatory actions of VIP and PACAP suggest these peptides may not only regulate intrathalamic rhythmic activities, but also may influence information transfer through thalamocortical circuits.

scholarly journals Adult loss of Cacna1a in mice recapitulates childhood absence epilepsy by distinct thalamic bursting mechanisms

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 161-174 ◽  
Author(s):  
Qing-Long Miao ◽  
Stefan Herlitze ◽  
Melanie D Mark ◽  
Jeffrey L Noebels
Keyword(s):  
Developmental Plasticity ◽  
Absence Epilepsy ◽  
Adult Brain ◽  
Burst Firing ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Adult Onset ◽  
Childhood Absence Epilepsy ◽  
Loss Of Function ◽  
Relay Neurons

Abstract Inborn errors of CACNA1A-encoded P/Q-type calcium channels impair synaptic transmission, producing early and lifelong neurological deficits, including childhood absence epilepsy, ataxia and dystonia. Whether these impairments owe their pathologies to defective channel function during the critical period for thalamic network stabilization in immature brain remains unclear. Here we show that mice with tamoxifen-induced adult-onset ablation of P/Q channel alpha subunit (iKOp/q) display identical patterns of dysfunction, replicating the inborn loss-of-function phenotypes and, therefore demonstrate that these neurological defects do not rely upon developmental abnormality. Unexpectedly, unlike the inborn model, the adult-onset pattern of excitability changes believed to be pathogenic within the thalamic network is non-canonical. Specifically, adult ablation of P/Q channels does not promote Cacna1g-mediated burst firing or T-type calcium current (IT) in the thalamocortical relay neurons; however, burst firing in thalamocortical relay neurons remains essential as iKOp/q mice generated on a Cacna1g deleted background show substantially diminished seizure generation. Moreover, in thalamic reticular nucleus neurons, burst firing is impaired accompanied by attenuated IT. Interestingly, inborn deletion of thalamic reticular nucleus-enriched, human childhood absence epilepsy-linked gene Cacna1h in iKOp/q mice reduces thalamic reticular nucleus burst firing and promotes rather than reduces seizure, indicating an epileptogenic role for loss-of-function Cacna1h gene variants reported in human childhood absence epilepsy cases. Together, our results demonstrate that P/Q channels remain critical for maintaining normal thalamocortical oscillations and motor control in the adult brain, and suggest that the developmental plasticity of membrane currents regulating pathological rhythmicity is both degenerate and age-dependent.

Comparing GABAergic cell populations in the thalamic reticular nucleus of normal and genetic absence epilepsy rats from Strasbourg (GAERS)

2013 ◽  
Vol 34 (11) ◽  
pp. 1991-2000 ◽  
Author(s):  
Safiye Çavdar ◽  
Hüsniye Hacıoğlu Bay ◽  
Özlem Kirazlı ◽  
Yusuf Özgür Çakmak ◽  
Filiz Onat
Keyword(s):  
Absence Epilepsy ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Cell Populations

Excitatory Actions of Dopamine Via D1-Like Receptors in the Rat Lateral Geniculate Nucleus

2005 ◽  
Vol 94 (6) ◽  
pp. 3708-3718 ◽  
Author(s):  
G. Govindaiah ◽  
Charles L. Cox
Keyword(s):  
Visual Information ◽  
Information Transfer ◽  
Neuronal Excitability ◽  
Slow Wave Sleep ◽  
Membrane Depolarization ◽  
Dopamine Receptor Agonist ◽  
Cation Current ◽  
Cell Recording ◽  
Specific Antagonist ◽  
Relay Neurons

The excitability of relay neurons in the dorsal geniculate nucleus (dLGN) can be altered by a variety of neuromodulators. The dLGN receives substantial dopaminergic input from the brain stem, and this innervation may play a crucial role in the gating of visual information from the retina to visual neocortex. In this study, we investigated the action of dopamine on identified dLGN neurons using whole cell recording techniques. Dopamine (2–200 μM) produced a membrane depolarization in >95% of relay neurons tested but did not alter excitability of dLGN interneurons. The D1-like dopamine receptor agonist SKF38393 (2–50 μM) produced a similar depolarization in dLGN relay neurons. However, the D2-like receptor agonists, bromocriptine (25–50 μM) and PPHT (1–50 μM), did not alter the membrane potential of relay neurons. SCH23390 (5–10 μM), a D1-like receptor antagonist, attenuated the depolarizing actions of both dopamine and SKF38393 . Furthermore, the excitatory actions of dopamine and SKF38393 were attenuated by ZD7288, a specific antagonist for the hyperpolarization activated mixed cation current, Ih. Our data suggest that dopamine, acting via D1-like receptors, activates Ih leading to a membrane depolarization. Through the modulation of dLGN neuronal excitability, ascending and descending activating systems may not only control the state of the thalamus such as the transition from slow-wave sleep to waking but also regulate the efficacy of information transfer during waking states.

scholarly journals Two classes of excitatory synaptic responses in rat thalamic reticular neurons

2016 ◽  
Vol 116 (3) ◽  
pp. 995-1011 ◽  
Author(s):  
Charlotte Deleuze ◽  
John R. Huguenard
Keyword(s):  
Nmda Receptors ◽  
Sensory Processing ◽  
Clustering Algorithm ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Reticular Cell ◽  
Reticular Neurons ◽  
Relay Neurons

The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-d-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg2+-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and thalamocortical oscillations.

Self–sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABAA receptor potentials

10.1038/5729 ◽  
1999 ◽  
Vol 2 (2) ◽  
pp. 168-174 ◽  
Author(s):  
M. Bazhenov ◽  
I. Timofeev ◽  
M. Steriade ◽  
T.J. Sejnowski
Keyword(s):  
Gabaa Receptor ◽  
Rhythmic Activity ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus

No loss in total neuron number in the thalamic reticular nucleus and neocortex in the genetic absence epilepsy rats from Strasbourg

1996 ◽  
Vol 26 (1) ◽  
pp. 45-48 ◽  
Author(s):  
Anne Sabers ◽  
Arne Møller ◽  
Jørgen Scheel-Krüger ◽  
Agnete Mouritzen Dam
Keyword(s):  
Absence Epilepsy ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Neuron Number

Does the ascending cholinergic projection inhibit or excite neurons in the rat thalamic reticular nucleus?

1986 ◽  
Vol 56 (5) ◽  
pp. 1310-1320 ◽  
Author(s):  
Y. Kayama ◽  
I. Sumitomo ◽  
T. Ogawa
Keyword(s):  
Cholinergic Neurons ◽  
Sensory Stimulation ◽  
Thalamic Reticular Nucleus ◽  
Resting Potential ◽  
Reticular Nucleus ◽  
Laterodorsal Tegmental Nucleus ◽  
Unit Recording ◽  
Tonic Firing ◽  
Tegmental Nucleus ◽  
Low Threshold

In rats anesthetized with urethan, neuronal activity was recorded in those portions of the thalamic reticular nucleus (TR) excitable by visual, somatosensory, or auditory input. Observations were made on changes in rate and pattern of discharge of these neurons during repetitive stimulation of the laterodorsal tegmental nucleus (LDT), which is composed of cholinergic neurons projecting to the thalamus. In general, TR neurons showed spontaneous activity consisting of sporadic bursts of several spikes and responded to sensory stimulation with bursts of spikes which repeated several times. Weak LDT stimulation depressed or eliminated the occurrence of both spontaneous and evoked burst discharges. When LDT stimulation was sufficiently strong, however, the majority of TR neurons resumed their tonic discharges. In some animals the cortical EEG was recorded simultaneously with unit recording in TR. Suppression of burst discharges in TR was obtained even with LDT stimulation weaker than the threshold for desynchronizing the EEG. The induction of tonic discharge, on the other hand, required stimulation strong enough to produce desynchronization. The effects of LDT stimulation, such as the suppression of bursts and the induction of tonic discharge, were mimicked by acetylcholine and were antagonized by scopolamine, both drugs being applied ionophoretically. Cooling of the visual cortex abolished LDT-induced tonic discharges of visual TR neurons. A recent report and our preliminary observation show that, when the resting potential is relatively hyperpolarized, TR neurons generated a burst of spikes superposed on a low-threshold broad spike, which is inactivated and replaced with tonic firing by depolarization. Supported by these facts, the present results suggest that cholinergic input depolarizes TR neurons directly and that further depolarization occurs indirectly via activated cortex when the LDT stimulation is sufficiently strong to desynchronize EEG.

scholarly journals TRPM4 conductances in thalamic reticular nucleus neurons generate persistent firing during slow oscillations

2020 ◽  
Author(s):  
John J. O’Malley ◽  
Frederik Seibt ◽  
Jeannie Chin ◽  
Michael Beierlein
Keyword(s):  
Rhythmic Activity ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Plateau Potentials ◽  
Slow Oscillations ◽  
Synaptic Circuits ◽  
Ventrobasal Thalamus ◽  
Persistent Firing

AbstractDuring sleep, neurons in the thalamic reticular nucleus (TRN) participate in distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory relay nuclei are known to underlie the generation of sleep spindles, the mechanisms regulating slow (<1 Hz) forms of thalamic oscillations are not well understood. Under in vitro conditions, TRN neurons can generate slow oscillations in a cell-intrinsic manner, with postsynaptic Group 1 metabotropic glutamate receptor (mGluR) activation leading to the generation of plateau potentials mediated by both T-type Ca2+ currents and Ca2+ -activated nonselective cation currents (ICAN). However, the identity of ICAN and the possible contribution of thalamic circuits to slow rhythmic activity remain unclear. Using thalamic slices derived from adult mice of either sex, we recorded slow forms of rhythmic activity in TRN neurons, which were mediated by fast glutamatergic thalamoreticular inputs but did not require postsynaptic mGluR activation. For a significant fraction of TRN neurons, synaptic inputs or brief depolarizing current steps led to long-lasting plateau potentials and persistent firing (PF), and in turn, resulted in sustained synaptic inhibition in postsynaptic relay neurons of the ventrobasal thalamus (VB). Pharmacological approaches indicated that plateau potentials were triggered by Ca2+ influx through T-type Ca2+ channels and mediated by Ca2+ and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, our results suggest that thalamic circuits can generate slow oscillatory activity, mediated by an interplay of TRN-VB synaptic circuits that generate rhythmicity and TRN cell-intrinsic mechanisms that control PF and oscillation frequency.Significance StatementSlow forms of thalamocortical rhythmic activity are thought to be essential for memory consolidation during sleep and the efficient removal of potentially toxic metabolites. In vivo, thalamic slow oscillations are regulated by strong bidirectional synaptic pathways linking neocortex and thalamus. Therefore, in vitro studies in the isolated thalamus can offer important insights about the ability of individual neurons and local circuits to generate different forms of rhythmic activity. We found that circuits formed by GABAergic neurons in the thalamic reticular nucleus (TRN) and glutamatergic relay neurons in the ventrobasal thalamus generated slow oscillatory activity, which was accompanied by persistent firing in TRN neurons. Our results identify both cell-intrinsic and synaptic mechanisms that mediate slow forms of rhythmic activity in thalamic circuits.

scholarly journals Modulation of Inhibitory Activity by Nitric Oxide in the Thalamus

2007 ◽  
Vol 97 (5) ◽  
pp. 3386-3395 ◽  
Author(s):  
Sunggu Yang ◽  
Charles L. Cox
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Activity ◽  
Visual Information ◽  
Information Transfer ◽  
Inhibitory Neurons ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
No Production ◽  
No Donor

The dorsal lateral geniculate nucleus (dLGN) is essential for the transfer of visual information from the retina to visual cortex, and inhibitory mechanisms can play a critical in regulating such information transfer. Nitric oxide (NO) is an atypical neuromodulator that is released in gaseous form and can alter neural activity without direct synaptic connections. Nitric oxide synthase (NOS), an essential enzyme for NO production, is localized in thalamic inhibitory neurons and cholinergic brain stem neurons that innervate the thalamus, although NO-mediated effects on thalamic inhibitory activity remain unknown. We investigated NO effects on inhibitory activity in dLGN using an in vitro slice preparation. The NO donor, SNAP, selectively potentiated the frequency, but not amplitude, of spontaneous inhibitory postsynaptic currents (sIPSCs) in thalamocortical relay neurons. This increase also persisted in tetrodotoxin (TTX), consistent with an increase in GABA release from presynaptic terminals. The SNAP-mediated actions were attenuated not only by the NO scavenger carboxy-PTIO but also by the guanylyl cyclase inhibitor ODQ. The endogenous NO precursor l-arginine produced actions similar to those of SNAP on sIPSC activity and these l-arginine–mediated actions were attenuated by the NOS inhibitor L-NMMA acetate. The SNAP-mediated increase in sIPSC activity was observed in both dLGN and ventrobasal thalamic nucleus (VB) neurons. Considering the lack of interneurons in rodent VB, the NO-mediated actions likely involve an increase in the output of axon terminals of thalamic reticular nucleus neurons. Our results indicate that NO upregulates thalamic inhibitory activity and thus these actions likely influence sensory information transfer through thalamocortical circuits.

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