Thalamic Relay Nuclei Research Articles

Functionally Distinct Circuits Are Linked by Heterocellular Electrical Synapses in the Thalamic Reticular Nucleus.

The thalamic reticular nucleus (TRN) inhibits sensory thalamocortical relay neurons and is a key regulator of sensory attention as well as sleep and wake states. Recent developments have identified two distinct genetic subtypes of TRN neurons, calbindin-expressing (CB) and somatostatin-expressing (SOM) neurons. These subtypes differ in localization within the TRN, electrophysiological properties, and importantly, targeting of thalamocortical relay channels. CB neurons send inhibition to and receive excitation from first-order thalamic relay nuclei, while SOM neurons send inhibition to and receive excitation from higher-order thalamic areas. These differences create distinct channels of information flow. It is unknown whether TRN neurons form electrical synapses between SOM and CB neurons and consequently bridge first-order and higher-order thalamic channels. Here, we use GFP reporter mice to label and record from CB-expressing and SOM-expressing TRN neurons. We confirm that GFP expression properly differentiates TRN subtypes based on electrophysiological differences, and we identified electrical synapses between pairs of neurons with and without common GFP expression for both CB and SOM types. That is, electrical synapses link both within and across subtypes of neurons in the TRN, forming either homocellular or heterocellular synapses. Therefore, we conclude that electrical synapses within the TRN provide a substrate for functionally linking thalamocortical first-order and higher-order channels within the TRN.

Suppression of seizure in childhood absence epilepsy using robust control of deep brain stimulation: a simulation study

Deep brain stimulation (DBS) is a promising technique to relieve the symptoms in patients with intractable seizures. Although the DBS therapy for seizure suppression dates back more than 40 years, determining stimulation parameters is a significant challenge to the success of this technique. One solution to this challenge with application in a real DBS system is to design a closed-loop control system to regulate the stimulation intensity using computational models of epilepsy automatically. The main goal of the current study is to develop a robust control technique based on adaptive fuzzy terminal sliding mode control (AFTSMC) for eliminating the oscillatory spiking behavior in childhood absence epilepsy (CAE) dynamical model consisting of cortical, thalamic relay, and reticular nuclei neurons. To this end, the membrane voltage dynamics of the three coupled neurons are considered as a three-input three-output nonlinear state delay system. A fuzzy logic system is developed to estimate the unknown nonlinear dynamics of the current and delayed states of the model embedded in the control input. Chattering-free control input (continuous DBS pulses) without any singularity problem is the superiority of the proposed control method. To guarantee the bounded stability of the closed-loop system in a finite time, the upper bounds of the external disturbance and minimum estimation errors are updated online with adaptive laws without any offline tuning phase. Simulation results are provided to show the robustness of AFTSMC in the presence of uncertainty and external disturbances.

Dynamic mechanism of epileptic seizures induced by excitatory pyramidal neuronal population

<abstract><p>The pyramidal neuronal population (PY) in the cerebral cortex is closely related to epilepsy, while the excitability of PY is directly affected by the excitatory interneurons (EIN), the inhibitory interneurons (IN), and the thalamic relay nucleus (TC). Based on this, we use the thalamocortical neural field model to explore the dynamic mechanism of system transition by taking the synaptic connection strengths of the above three nuclei on PY as the main factor affecting seizures. The results show that the excitatory effects of EIN on PY induce transitions from 1-spike and wave discharges (SWDs) to 2-spike and wave discharges (2-SWDs), the inhibitory effects of IN on PY induce transitions from saturated state to tonic oscillation state, and the excitatory effects of TC on PY induce transitions from clonic oscillation state to saturated state. According to the single-parameter bifurcation analysis, it is found that Hopf and fold limit cycle bifurcations are the key factors leading to the state transition. In addition, the state analysis of the three pathways is carried out in pairs. The results show that the system produces more types of epileptic seizures with the combined action of EIN and TC on PY. According to the two-parameter bifurcation curve, we obtain the stable parameter areas of tonic-clonic oscillations, SWDs, 2-SWDs and saturated discharges, and clearly find the reasonable transition path between tonic-clonic seizures and absence seizures. This may provide some theoretical guidance for the transmission and evolution of seizures.</p></abstract>

Role of coupling distances in a coupled thalamocortical network in the treatment of epilepsy

The establishment of a recent theoretical model of a coupled cortical thalamic network is an important step in the spatiotemporal dynamics of the brain. However, choosing the coupling distances and parameters for deep brain stimulation remains a very challenging task. This study aimed to establish a coupled cortical thalamic model with uncertain coupling distances. Utilizing different pathways formed by the pyramidal neuronal population, thalamic reticular nucleus, and thalamic relay nucleus, we reduced epileptic seizures with spike-wave discharges (SWDs) at 2–4 Hz. In modelling terms, numerical simulations demonstrated that a combination (1/3, 1/9) of the left and right ventricles is the optimal coupling distance of the proposed model by analyzing the percentage of SWDs. In simulation terms, on the one hand, the number of SWDs is inversely proportional to the amplitude; on the other hand, the number of SWDs shows a U-shaped trend with the change in frequency. The present study provides an important theoretical basis and direction for the future treatment of absence epilepsy. In brief, our simulation results will hopefully provide some help to patients.

The Critical Modulatory Role of Spiny Stellate Cells in Seizure Onset Based on Dynamic Analysis of a Neural Mass Model.

Growing evidence suggests that excitatory neurons in the brain play a significant role in seizure generation. Nonetheless, spiny stellate cells are cortical excitatory non-pyramidal neurons in the brain, whose basic role in seizure occurrence is not well understood. In the present research, we study the critical role of spiny stellate cells or the excitatory interneurons (EI), for the first time, in epileptic seizure generation using an extended neural mass model inspired by a thalamocortical model originally introduced by another research group. Applying bifurcation analysis on this modified model, we investigated the rich dynamics corresponding to the epileptic seizure onset and transition between interictal and ictal states caused by EI connectivity to other cell types. Our results indicate that the transition between interictal and ictal states (preictal signal) corresponds to a supercritical Hopf bifurcation, and thus, the extended model suggests that before seizure onset, the amplitude and frequency of neural activities gradually increase. Moreover, we showed that (1) the altered function of GABAergic and glutamatergic receptors of EI can cause seizure, and (2) the pathway between the thalamic relay nucleus and EI facilitates the transition from interictal to ictal activity by decreasing the preictal period. Thereafter, we considered both sensory and cortical periodic inputs to study model responses to various harmonic stimulations. Bifurcation analysis of the model, in this case, suggests that the initial state of the model might be the main cause for the transition between interictal and ictal states as the stimulus frequency changes. The extended thalamocortical model shows also that the amplitude jump phenomenon and non-linear resonance behavior result from the preictal state of the modified model. These results can be considered as a step forward to a deeper understanding of the mechanisms underlying the transition from normal activities to epileptic activities.

072 Sleep Spindle Harmonics in Insomnia

Abstract Introduction Prior research has reported NREM spectral EEG differences between individuals with insomnia and good-sleeper controls, including elevated high-frequency EEG power (beta/gamma bands, ~16-50Hz) and, to a lesser extent, elevations in sleep spindle parameters. However, the mechanisms driving these differences remain unclear. Harmonics have been observed in EEG data as spectral peaks at multiples of a fundamental frequency associated with an event (e.g., for a 14Hz spindle, the 2nd harmonic is expected to be a peak at 28Hz). Thus far, there has been very limited application of this idea of spectral harmonics to sleep spindles, even though these patterns can indeed be seen in some existing literature. We sought to build on this literature to apply spectral harmonic analysis to better understand differences between insomnia and good sleepers. Methods 15 individuals with insomnia disorder (DSM-5 criteria, 13 female, age 18–32 years) and 15 good-sleeper controls (matched for sex, age, and BMI) completed an overnight polysomnography recording in the laboratory and subsequent daytime testing. Insomnia diagnosis was determined by a board-certified sleep specialist, and exclusion criteria included psychiatric history within past 6 months, other sleep disorders, significant medical conditions, and medications with significant effects on inflammation, autonomic function, or other psychotropic effects. Results Consistent with prior studies, we found elevated sleep spindle density and fast sigma power (14-16Hz). Despite no difference in beta or gamma band power when averaged across NREM sleep, time-frequency analysis centered on the peaks of detected spindles revealed a phasic elevation in spectral power surrounding the 28Hz harmonic peak in the insomnia group, especially for spindles coupled with slow waves. We also observed an overall pattern of time-locked delay in the 28Hz harmonic peak, occurring approximately 40 msec after spindle peaks. Furthermore, we observed a 42Hz ‘3rd harmonic’ peak, not yet predicted by the existing modeling work, which was also elevated for insomnia. Conclusion In conjunction with existing mathematical modeling work that has linked sleep spindle harmonic peaks with thalamic relay nuclei as the primary generators of this EEG signature, these findings may enable novel insights into specific thalamocortical mechanisms of insomnia and non-restorative sleep. Support (if any) NIH 5T32HL007901-22

Rostral Intralaminar Thalamus Engagement in Cognition and Behavior.

The thalamic rostral intralaminar nuclei (rILN) are a contiguous band of neurons that include the central medial, paracentral, and central lateral nuclei. The rILN differ from both thalamic relay nuclei, such as the lateral geniculate nucleus, and caudal intralaminar nuclei, such as the parafascicular nucleus, in afferent and efferent connectivity as well as physiological and synaptic properties. rILN activity is associated with a range of neural functions and behaviors, including arousal, pain, executive function, and action control. Here, we review this evidence supporting a role for the rILN in integrating arousal, executive and motor feedback information. In light of rILN projections out to the striatum, amygdala, and sensory as well as executive cortices, we propose that such a function enables the rILN to modulate cognitive and motor resources to meet task-dependent behavioral engagement demands.

Dynamic Transitions of Epilepsy Waveforms Induced by Astrocyte Dysfunction and Electrical Stimulation.

Experimental studies have shown that astrocytes participate in epilepsy through inducing the release of glutamate. Meanwhile, considering the disinhibition circuit among inhibitory neuronal populations with different time scales and the feedforward inhibition connection from thalamic relay nucleus to cortical inhibitory neuronal population, here, we propose a modified thalamocortical field model to systematically investigate the mechanism of epilepsy. Firstly, our results show that rich firing activities can be induced by astrocyte dysfunction, including high or low saturated state, high- or low-frequency clonic, spike-wave discharge (SWD), and tonic. More importantly, with the enhancement of feedforward inhibition connection, SWD and tonic oscillations will disappear. In other words, all these pathological waveforms can be suppressed or eliminated. Then, we explore the control effects after different external stimulations applying to thalamic neuronal population. We find that single-pulse stimulation can not only suppress but also induce pathological firing patterns, such as SWD, tonic, and clonic oscillations. And we further verify that deep brain stimulation can control absence epilepsy by regulating the amplitude and pulse width of stimulation. In addition, based on our modified model, 3 : 2 coordinated reset stimulation strategies with different intensities are compared and a more effective and safer stimulation mode is proposed. Our conclusions are expected to give more theoretical insights into the treatment of epilepsy.

Possible pathological mechanisms of absence seizures appearing in the reticular thalamic nucleus: A theoretical basis

In this paper, we study the generation and inhibition mechanisms of absence epilepsy appearing in the reticular thalamic nucleus (TRN) of the thalamus in a basal ganglia-corticothalamic network, which has been proven to be effective for simulating epileptic seizures in the brain. We found that the spike-and-wave discharges (SWDs) activities (2–4 Hz) appeared in the TRN by adjusting the coupling weight in the excitatory pathway “SRN ⟶ EPN” and the delay in the inhibitory pathway “TRN ⊸ Thalamic relay nucleus (SRN)”. The SWDs can disappear by controlling the firing state of the substantia nigra pars reticulata (SNr), which sends strong inhibitory projections to both the SRN and TRN in the model. Suppression of seizure activities may be realized through both the isolated pathway “SNr ⊸ TRN” and the isolated pathway “SNr ⊸ SRN”, or through the competition mechanism between them. Unidirectional and bidirectional regulation phenomena were obtained in the simulations, and the mechanisms of these can be well explained in this model. The theoretical mechanism of epilepsy appearing in the TRN has received little attention to date, and we hope that the results shown in this paper can inspire new ideas for experimental study in the future.

Non-invasive High Frequency Repetitive Transcranial Magnetic Stimulation (hfrTMS) Robustly Activates Molecular Pathways Implicated in Neuronal Growth and Synaptic Plasticity in Select Populations of Neurons.

Patterns of neuronal activity that induce synaptic plasticity and memory storage activate kinase cascades in neurons that are thought to be part of the mechanism for synaptic modification. One such cascade involves induction of phosphorylation of ribosomal protein S6 in neurons due to synaptic activation of AKT/mTOR and via a different pathway, activation of MAP kinase/ERK1/2. Here, we show that phosphorylation of ribosomal protein S6 can also be strongly activated by high frequency repetitive transcranial magnetic stimulation (hfrTMS). HfrTMS was delivered to lightly anesthetized rats using a stimulation protocol that is a standard for inducing LTP in the perforant path in vivo (trains of 8 pulses at 400 Hz repeated at intervals of 1/10 s). Stimulation produced stimulus-locked motor responses but did not elicit behavioral seizures either during or after stimulation. After as little as 10 min of hfrTMS, immunostaining using phospho-specific antibodies for the phosphorylated form of ribosomal protein S6 (rpS6) revealed robust induction of rpS6 phosphorylation in large numbers of neurons in the cortex, especially the piriform cortex, and also in thalamic relay nuclei. Quantification revealed that the extent of the increased immunostaining depended on the number of trains and stimulus intensity. Of note, immunostaining for the immediate early genes Arc and c-fos revealed strong induction of IEG expression in many of the same populations of neurons throughout the cortex, but not the thalamus. These results indicate that hfrTMS can robustly activate molecular pathways critical for plasticity, which may contribute to the beneficial effects of TMS on recovery following brain and spinal cord injury and symptom amelioration in human psychiatric disorders. These molecular processes may be a useful surrogate marker to allow optimization of TMS parameters for maximal therapeutic benefit.

Alpha rhythm slowing in a modified thalamo-cortico-thalamic model related with Alzheimer's disease.

A decrease in alpha band power is defined as a hallmark of electroencephalogram (EEG) in Alzheimer’s disease (AD). This study devotes to understanding the neuronal correlates of alpha rhythm slowing associated with AD from the view of neurocomputation. Firstly, a modified computational model of thalamo-cortico-thalamic (TCT) circuitry is constructed by incorporating two important biologically plausible ingredients. One is the disinhibition property between different inhibitory interneurons in the cortical module. The other is the full relay function of thalamic relay nucleus (TCR) to the cortical module. Then, by decreasing synaptic connectivity parameters to mimic the neuropathological condition of synapse loss in AD, the correlation between neuronal synaptic behavior and abnormal alpha rhythm is simulated by means of power spectral analysis. The results indicate that these decreases of synaptic activity, i.e., not only the excitatory synaptic connections from TCR to fast inhibitory interneurons Cfte and from excitatory interneurons to pyramidal neurons Cpxe but also the inhibitory synaptic connections from fast inhibitory interneurons to slow inhibitory interneurons Clfi and from inhibitory interneurons to TCR Ctii, can significantly diminish the peak power density over the alpha band of the thalamic output, which implies that there is a slowing of alpha band. Furthermore, the underlying mechanism behind the alpha rhythmic changes is analyzed using nonlinear dynamical technique. The results reveal that decreases of Cfte, Cpxe, Clfi and Ctii can make the thalamic module transfer from a limit cycle mode to a point attractor mode, which may lead to the alpha rhythm slowing in the modified TCT model. We expect this work can be helpful in identifying early biomarkers of AD’s EEG and understanding potential pathogenesis of AD.

Mouse BOLD fMRI at ultrahigh field detects somatosensory networks including thalamic nuclei

Forepaw somatosensory stimulation induces neural activities in relay thalamic nuclei, the primary somatosensory cortex of forelimb (S1FL), and the secondary somatosensory cortex (S2). However, rodent fMRI studies of somatosensory stimulation have commonly reported BOLD changes only in S1FL, which may be due to side effects of anesthetics and/or the low sensitivity in the thalamus. Thus, we have obtained mouse BOLD fMRI under newly-adopted ketamine-xylazine anesthesia. High-resolution BOLD fMRI obtained with same imaging parameters at 9.4T versus 15.2T shows the improvement of functional detectability by ≥ 2 times at 15.2T due to higher signal intensity and larger BOLD response. The fMRI responses at 15.2T were robustly observed at well-known somatosensory networks including thalamus. Second, echo-time-dependent BOLD signals are dominant based on multi-echo fMRI data. A ratio of BOLD responses in S1FL to thalamus is ∼2, which is not related to different baseline T2∗ or different cerebral blood volume. Third, group-averaged 15.2T BOLD maps show activities in S1FL, S2, motor cortices, and thalamic nuclei, which agree well with neural tracing network data from the Allen Institute, demonstrating that fMRI detects entire somatosensory networks. Our data suggest that ultrahigh field fMRI provides a unique window into understanding functional networks in normal and transgenic mouse models noninvasively.

Cell‐type specific expression of GluN2C and GluN2D subunits and their role in schizophrenic phenotypes

IntroductionFunctional deficit in NMDA‐receptors on parvalbumin (PV)‐positive interneurons (PV‐NMDARs) is central to the pathophysiology of schizophrenia. NMDA channel blockers like ketamine and MK‐801 have shown to produce psychosis by inhibiting GluN2C and GluN2D subunits with greater affinity than other subunits. Recent neuroanatomical and electrophysiological studies have reported expression of GluN2D subunit in PV positive interneurons in corticolimbic regions but the precise distribution of GluN2C subunit especially in PV interneurons remains unknown.Hence, the objective of the study was to identify the expression pattern of GluN2C subunit in neuronal and non‐neuronal cell population and to perform a side‐by‐side comparison of the effect of partial and complete ablation of GluN2C and GluN2D subunit on pure C57BL/6N mouse strain.Methods and ResultsImmunohistochemistry was used to determine the heterogenous expression of GluN2C using a novel eGFP reporter mouse model. We found the expression of EGFP (GluN2C) with PV positive neurons in nucleus reticularis of the thalamus, globus pallidus externa and interna, ventral pallidum and substantia nigra. Interestingly, EGFP (GluN2C) showed co‐localization with astrocytic marker in the striatum, cortex, hippocampus and amygdala but not with PV positive neurons. GluN2C was found to be enriched in several thalamic relay nuclei including first order and higher order nuclei. GluN2D knockout mouse exhibited hypo‐locomotion and anxiety‐like behavior in the open field test. We found a significant increase in startle amplitude in GluN2C HET but not GluN2C KO and no change in prepulse inhibition (PPI) in either genotype was observed. Increase in startle response was found for GluN2D heterozygous and GluN2D knockout along with lower prepulse inhibition at some decibels. We also found CIQ, a selective positive allosteric modulator for GluN2C/GluN2D subunit, reversed the MK801 induced impairment in PPI in GluN2C wildtype and heterozygous mice but not in GluN2C KO mice. Furthermore, we observed that GluN2C knockout mice but not GluN2D knockout mice were less sensitive to phencyclidine‐induced hyperlocomotion, a model of psychosis. The cell‐type specific expression of both GluN2C and GluN2D subunit may provide more insights into schizophrenia‐like behaviors. Hence, we will confirm psychotic and sensorimotor deficits by selectively deleting GluN2D subunit from PV‐positive interneurons and GluN2C subunit from astrocytes using Cre‐lox strategy.ConclusionTogether, these results identify the unique expression pattern of GluN2C subunit in neuronal and non‐neuronal cell population. It also demonstrates the preferential involvement of GluN2C‐ containing receptors in phencyclidine‐induced hyperlocomotion and that facilitation of GluN2C subunit may reverse the schizophrenic phenotypes.Support or Funding InformationR21 NS104705This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Outgrowing seizures in Childhood Absence Epilepsy: time delays and bistability.

We formulate a conductance-based model for a 3-neuron motif associated with Childhood Absence Epilepsy (CAE). The motif consists of neurons from the thalamic relay (TC) and reticular nuclei (RT) and the cortex (CT). We focus on a genetic defect common to the mouse homolog of CAE which is associated with loss of GABAA receptors on the TC neuron, and the fact that myelination of axons as children age can increase the conduction velocity between neurons. We show the combination of low GABAA mediated inhibition of TC neurons and the long corticothalamic loop delay gives rise to a variety of complex dynamics in the motif, including bistability. This bistability disappears as the corticothalamic conduction delay shortens even though GABAA activity remains impaired. Thus the combination of deficient GABAA activity and changing axonal myelination in the corticothalamic loop may be sufficient to account for the clinical course of CAE.

Peter Orlebar Bishop. 14 June 1917—3 June 2012

Peter Orlebar Bishop was an Australian neurophysiologist renowned for his ingenious quantitative approach to the study of the mammalian visual system and his great ability to attract a large number of talented people to visual research. Peter’s research was based on specially designed, precise instrumentation and data quantification applied mainly to analysis of the response properties of single neurones in the principal dorsal thalamic visual relay nucleus, the dorsal lateral geniculate nucleus (LGNd) and the primary visual cortex. This quantitative bent was evident throughout Peter’s entire research career: starting with the design and construction of innovative DC amplifiers; to his quantitative analysis of optics, ‘schematic eye’ for the cat, which rivalled Gullstrand’s schematic eye for humans; to creating and demonstrating validity of the concept of ‘projection lines’ in the representation of contralateral visual field in different cellular layers of the LGNd of mammals with frontally positioned eyes and discovery of massive binocular input to single LGNd neurones. Peter’s engineering approach was probably at its heuristic peak when it revealed many details of binocular interactions at the level of single neurones in the primary visual cortex—the interactions which appear to underpin overall mechanisms underlying stereopsis, the high precision binocular depth sense.

The generation mechanism of spike-and-slow wave discharges appearing on thalamic relay nuclei

In this paper, we use a model modified from classic corticothalamic network(CT) to explore the mechanism of absence seizures appearing on specific relay nuclei (SRN) of the thalamus. It is found that typical seizure states appear on SRN through tuning several critical connection strengths in the model. In view of previous experimental and theoretical works which were mainly on epilepsy seizure phenomena appearing on excitatory pyramidal neurons (EPN) of the cortex, this is a novel model to consider the seizure observed on thalamus. In particular, the onset mechanism is different from previous theoretical studies. Inspired by some previous clinical and experimental studies, we employ the external stimuli voltage on EPN and SRN in the network, and observe that the seizure can be well inhibited by tuning the stimulus intensity appropriately. We further explore the effect of the signal transmission delays on seizures, and found that the polyspike phenomenon appears only when the delay is sufficiently large. The experimental data also confirmed our model. Since there is a complex network in the brain and all organizations are interacting closely with each other, the results obtained in this paper provide not only biological insights into the regulatory mechanisms but also a reference for the prevention and treatment of epilepsy in future.

Peter Orlebar Bishop 1917–2012

Peter Orlebar Bishop was an Australian neurophysiologist renowned for his ingenious quantitative approach to study of the mammalian visual system and great ability to attract a large number of talented people to visual research. Peter's research was based on specially designed, precise instrumentation and data quantification applied mainly to analysis of the response properties of single neurones in the principal dorsal thalamic visual relay nucleus, the dorsal lateral geniculate nucleus (LGNd) and the primary visual cortex. This quantitative bent was evident throughout Bishop's entire research career:starting with the design and construction of innovative DC amplifiers; through to his quantitative analysis of optics—‘schematic eye' for the cat, which rivaled Gullstrand's schematic eye for humans; to creating and demonstrating validity of the concept of ‘projection lines' in the representation of contralateral visual field in different cellular layers of the LGNd of mammals with frontally positioned eyes and discovery of a very substantial binocular input to single LGNd neurones. The engineering approach of Peter was probably at its heuristic peak when it revealed many details of binocular interactions at the level of single neurones in the primary visual cortex—the interactions that appear to underpin overall mechanisms underlying stereopsis, the high precision binocular depth sense.

The neural basis of homeostatic and anticipatory thirst.

Water intake is one of the most basic physiological responses and is essential to sustain life. The perception of thirst has a critical role in controlling body fluid homeostasis and if neglected or dysregulated can lead to life-threatening pathologies. Clear evidence suggests that the perception of thirst occurs in higher-order centres, such as the anterior cingulate cortex (ACC) and insular cortex (IC), which receive information from midline thalamic relay nuclei. Multiple brain regions, notably circumventricular organs such as the organum vasculosum lamina terminalis (OVLT) and subfornical organ (SFO), monitor changes in blood osmolality, solute load and hormone circulation and are thought to orchestrate appropriate responses to maintain extracellular fluid near ideal set points by engaging the medial thalamic-ACC/IC network. Thirst has long been thought of as a negative homeostatic feedback response to increases in blood solute concentration or decreases in blood volume. However, emerging evidence suggests a clear role for thirst as a feedforward adaptive anticipatory response that precedes physiological challenges. These anticipatory responses are promoted by rises in core body temperature, food intake (prandial) and signals from the circadian clock. Feedforward signals are also important mediators of satiety, inhibiting thirst well before the physiological state is restored by fluid ingestion. In this Review, we discuss the importance of thirst for body fluid balance and outline our current understanding of the neural mechanisms that underlie the various types of homeostatic and anticipatory thirst.

Activation of Parvalbumin Neurons in the Rostro-Dorsal Sector of the Thalamic Reticular Nucleus Promotes Sensitivity to Pain in Mice

The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. In our study, the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain regulation was studied using chemogenetics based on designer receptors exclusively activated by designer drugs (DREADD). Then, projections from the TRNrd PV-positive neurons were explored using PV-Cre transgenic mice, conditional anterograde axonal tract tracing, and optogenetics, combined with immunohistochemistry and electrophysiology. The results showed that activation of PV-positive neurons in the TRNrd decreased the mechanical threshold and thermal latency of behaving mice during the light period when neuronal activity was low. Furthermore, the anterodorsal and paratenial thalamic nucleus received innervation from PV-positive neurons in the TRNrd. They were specifically inhibited by GABA, which is released from local axonal endings of PV neurons. These findings indicate that activation of PV neurons in the TRNrd increases pain sensitivity in PV-Cre transgenic mice.

K-complexes, spindles, and ERPs as impulse responses: unification via neural field theory.

To interrelate K-complexes, spindles, evoked response potentials (ERPs), and spontaneous electroencephalography (EEG) using neural field theory (NFT), physiology-based NFT of the corticothalamic system is used to model cortical excitatory and inhibitory populations and thalamic relay and reticular nuclei. The impulse response function of the model is used to predict the responses to impulses, which are compared with transient waveforms in sleep studies. Fits to empirical data then allow underlying brain physiology to be inferred and compared with other waves. Spontaneous K-complexes, spindles, and other transient waveforms can be reproduced using NFT by treating them as evoked responses to impulsive stimuli with brain parameters appropriate to spontaneous EEG in sleep stage 2. Using this approach, spontaneous K-complexes and sleep spindles can be analyzed using the same single theory as previously been used to account for waking ERPs and other EEG phenomena. As a result, NFT can explain a wide variety of transient waveforms that have only been phenomenologically classified to date. This enables noninvasive fitting to be used to infer underlying physiological parameters. This physiology-based model reproduces the time series of different transient EEG waveforms; it has previously reproduced experimental EEG spectra, and waking ERPs, and many other observations, thereby unifying transient sleep waveforms with these phenomena.