These studies in fetal monkeys and ferrets show that the two fundamental types of thalamic GABA neuron populate the thalamus during widely separated developmental epochs. Those of the ventral thalamus (VT) and epithalamus (ET) appear very early in conjunction with the GABA cells of the substantia nigra, globus pallidus, and pretectum (PT). GABA neurons intrinsic to the dorsal thalamus (DT) appear later, long after proliferative activity has ceased in the wall of the third ventricle, after dorsal thalamic nuclei have differentiated and at the same time as principal neurons are acquiring a glutamatergic phenotype. The exact origins of the two waves of GABA cells are uncertain but some appear to arrive from extrinsic sources that include the ganglionic eminence (GE) of the basal forebrain.

Intrathalamic oscillations related to sleep and epilepsy depend on interactions between synaptic mechanisms and intrinsic membrane excitability. One intrinsic conductance implicated in the genesis of thalamic oscillations is the H-current – a cationic current activated by membrane hyperpolarization. Activation of H-current promotes rebound excitation of thalamic relay neurons and can thus enhance recurrent network activity.

We examined the effects of H-current modulation on bicuculline-enhanced network oscillations (2–4 Hz) in rat thalamic slices. The adrenergic agonist norepinephrine, a known regulator of H-current, caused an alteration of the internal structure of the oscillations – they were enhanced and accelerated as the interval between bursts was shortened. The acceleration was blocked by the β-adrenergic antagonist propranolol. The β-agonist isoproterenol mimicked the effect of norepinephrine on oscillation frequency and truncated the responses suggesting that a β-adrenergic up-regulation of H-current modifies the internal structure (frequency) of thalamic oscillations. Consistent with this, we found that H-channel blockade by Cs+ or ZD7288 could decelerate the oscillations and produce more robust (longer lasting) responses. High concentrations of either Cs+ or ZD7288 blocked the oscillations.

These results indicate that a critical amount of H-current is necessary for optimal intrathalamic oscillations in the delta frequency range. Up- or down-regulation of H-current alter not only the oscillation frequency but also retard or promote the development of thalamic synchronous oscillations. This conclusion has important implications regarding the development of epilepsy in thalamocortical circuits.

Kainate receptors (KAR) remain the most poorly defined components of the glutamate receptor system in the CNS, mainly because of the difficulty of distinguishing currents gated by KAR from those mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor activation, and because KAR are expressed at significantly lower levels than AMPA receptors in most parts of the CNS.

The corticothalamic projection exerts its effects on thalamic neurons via NMDA, non-NMDA and metabotropic glutamate receptors. AMPA receptor mediated effects tend to predominate in the mature thalamus, but the involvement of kainate receptors at corticothalamic synapses on relay neurons and reticular nucleus neurons had not been studied.

The present work compared KAR influences on neurons in the ventral posterior nucleus (VP) and reticular nucleus (RTN), using whole-cell recording in P14–P20 mouse thalamocortical slices. The results were correlated with quantitative immuno-electron microscopic localization of kainate receptor sub-units at corticothalamic synapses in these nuclei. Small kainate-induced inward currents could be recorded in thalamic neurons in response to bath application of kainate, but no KAR-mediated pre-synaptic effects could be detected and no synaptic responses could be evoked in these cells by corticothalamic stimulation. Morphologically, GluR5/6/7 sub-units were expressed at low levels in both VP and RTN and were confined to post-synaptic membranes at corticothalamic synapses in both VP and RTN. Many synapses, however, lacked GluR5/6/7 immunoreactivity.

These results suggest that kainate receptor-mediated events are not major components of the responses of thalamic neurons to corticothalamic activation, either because of small numbers or their location in sites inaccessible to glutamate released from corticothalamic terminals.

The effects of different dendritic geometries and distal dendritic Na+ current distributions on the propagation of action potentials (APs) and sensory EPSPs were investigated using a multi-compartment model of thalamocortical (TC) neurones where the somatic and proximal dendritic distribution of voltage-gated channels matched the ones measured experimentally, i.e. a uniform distribution of K+ currents and a non-uniform distribution of Na+ and T-type Ca2+ currents.

Our simulations indicated that the distal dendritic Na+ channel density has not to be larger than 50% of the somatic density in order to reproduce the electrical activities recorded experimentally from the soma and proximal dendrites of TC neurones. Moreover, we could highlight the existence of a distinct threshold density of distal dendritic Na+ channels necessary to support the regeneration of APs in this part of the dendritic tree: this threshold density was smaller for non-branching than for heavily branching dendrites.

The amplitude of the somatic EPSP mainly depended on the number of simultaneously activated synapses on any dendritic branch, despite large differences in the size of the dendritic EPSPs. The amplitude of the EPSP on a proximal dendrite was also dependent on the number and relative location of simultaneously activated synapses on all other proximal dendritic branches. The dendritic geometry did not affect these features of the simulated sensory EPSPs. In addition, the duration of somatic and proximal dendritic EPSPs was markedly increased (100%) in the presence of somatic and proximal dendritic T-type Ca2+ current.

The backpropagation of EPSPs to distal dendrites was affected by the dendritic Na+ channel distributions, but even in the absence of distal dendritic Na+ channels the EPSP reached the dendritic ends with less than 40% decrease in amplitude. Overall, the amplitude of the backpropagating EPSP was not greatly affected by the dendritic geometry, though a smaller amplitude reduction in unbranched than in heavily branching dendrites was observed.

The interaction between cortical input frequency and intrinsic thalamic neuron (TN) properties were investigated using intracellular recordings from mice TNs in thalamocortical (TC) slices. Excitatory postsynaptic potentials (EPSPs) of corticothalamic (CT) origin were recorded at TN membrane potentials (Vm) held, by current clamp means, between −59 and −55 mV to avoid low-threshold calcium currents (IT) activation. EPSPs elicited in ventrobasal neurons (n = 25) by stimulation in the internal capsule showed constant latency, relatively fast rise time (2.9 ± 0.56 ms) and short duration (26.6 ± 9.11 ms). EPSPs evoked by threshold stimulation (n = 10) showed similar characteristics (mean rise time, 2.74 ± 0.42 ms; mean duration, 30 ± 8.00 ms). The time course of CT synaptic facilitation was determined using pairs of stimuli. Paired-pulse facilitation (PPF) of CT EPSPs peaked at 25–30 ms stimulus intervals and decayed exponentially with an average time constant of 130 ms (n = 50). Application of the NMDA receptor blocker APV (25 μM, n = 4) did not modify PPF for any interstimulus interval studied but suppressed frequency facilitation evoked by trains of CT stimuli. We compared the number of spikes per stimulus (Fs) evoked in TNs by repetitive CT stimulation over a range of frequencies at different Vm. At hyperpolarized Vm (below −65 mV) and frequencies of stimulation ≥ 10 Hz, Fs decreased along the train while at depolarized Vm (above −59 mV) Fs increased along the train. Decremental patterns resulted from the activation of IT while facilitatory patterns emerged from superposition of synaptic and intrinsic mechanisms. At hyperpolarized Vm, steady-state Fs was maximal for frequencies ≤ 2 Hz, intermediate for frequencies between 2 and 10 Hz and zero at ≥ 10 Hz. At depolarized Vm, steady-state Fs increased with increasing frequencies (from 1 to 40 Hz).

We conclude that the CT–TN junctions are tuned to establish stable thalamocortical resonant dynamics.

Neuroanatomical tracers were injected into two functionally distinct areas in the lateral sulcus of macaque monkeys, the parietal ventral area (PV) and the second somatosensory area (S2). Three of the four injection sites were electrophysiologically determined by defining the receptive fields of neurons at the injection site prior to the placement of the anatomical tracers. Additionally, all locations were confirmed myeloarchitectonically. Labeled cell bodies and axon terminals were identified in the ipsilateral dorsal thalamus and related to nuclear boundaries in tissue stained for cytochrome oxidase (CO) and Nissl substance. Our results indicate that PV receives substantial input from the inferior division of the ventral posterior nucleus (VPi), the anterior pulvinar (Pla), and from the ventral portion of the magnocellular division of the mediodorsal nucleus (MDm), which also is interconnected with prefrontal cortex, the entorhinal cortex and the amygdala. S2 receives input predominantly from VPi, the ventral posterior superior nucleus (VPs), and Pla. These results indicate that PV and S2 are involved in processing inputs from deep receptors in the muscles and joints. Because PV and S2 receive little if any cutaneous input from the thalamus, cutaneous input to these fields must arise mainly through cortical connections. Connectional data supports the proposition that PV and S2 integrate motor and somatic information necessary for proprioception, goal directed reaching and grasping and tactile object identification. Further, PV may play a role in tactile learning and memory.

Thalamic afferents and efferents primarily use the neurotransmitter glutamate, which acts through a variety of ionotropic (NMDA, AMPA, kainate) and metabotropic receptors. The NMDAR is composed of multiple subunits, NR1 and NR2A-D. The obligatory NRl subunit is expressed as one of eight isoforms, due to the alternative splicing of exons 5, 21, and 22. Each NRl splice variant is functionally distinct. For instance, alternative splicing of exons 21 and 22 renders two C-terminal variants, which differentially associate with NR2 subunits and intracellular molecules such the PSD-95 family of proteins. These PSD proteins play a pivotal role in NMDAR function by linking NMDARs to the cytoskeleton and downstream signal-transducing enzymes that can directly modulate NMDAR function and/or promote NMDAR-associated intracellular events.

Previous work reported that NRl is by far the most abundant NMDAR subunit expressed in the primate thalamus. In the current study, we extend these findings first by determining which NRl isoforms are predominantly expressed in the thalamus. Secondly, we characterize the expression of the NMDAR-associated PSD molecules, such as PSD-95, in the thalamus. Using in situ hybridization, we examined expression of the transcripts encoding NRl isoforms containing exons 5, 21, or 22, and transcripts encoding a set of the most well-characterized NMDAR-associated PSD proteins (NF-L, PSD93, PSD95, SAP102, and Yotiao). NRl exon 22-containing isoforms are the most abundant subunit transcripts, accounting for 40–50% of the NRl isoforms expressed in most thalamic nuclei. We also found that NF-L is by far the most abundant PSD protein expressed in the thalamus, followed by PSD-95, which is moderately and heterogeneously expressed. SAP102 and PSD-93 were expressed at moderate to low levels, with negligible amounts of Yotiao transcript expression. The PSD-95 family of molecules are critical for NMDAR function in the cell, and this study is the first to provide a detailed description of the expression of these molecules in primate thalamus. Our results demonstrate that NRl splice variants and associated PSD proteins are heterogeneously expressed across the thalamus, which is likely related to the intracellular events that occur in different thalamic nuclei.

The thalamus of the spiny rat Proechimys guyannensis (casiragua), a common rodent of the Amazon basin, was investigated with immunohistochemistry, using as markers GABA and glutamic acid decarboxylase, and calcium binding proteins. As in all mammals, GABAergic neurons containing also parvalbumin filled the reticular nucleus, and GABAergic cells were seen in the dorsal lateral geniculate nucleus. At variance with the laboratory rat, GABAergic and parvalbumin-containing neurons were also seen in the laterodorsal and anterodorsal nuclei, in which the two markers were co-distributed. Calbindin-immunopositive cells were widely distributed in dorsal thalamic domains, except for the intralaminar nuclei, and prevailed in the laterodorsal nucleus. The distribution of calretinin-immunopositive neurons was more restricted, and they were especially concentrated in the laterodorsal and midline nuclei.

At variance with the laboratory rat, in which systemic pilocarpine administration induces status epilepticus and results in chronic limbic epilepsy, pilocarpine elicited in casiragua an acute seizure that was not followed by spontaneous seizures up to 1 month, when changes were evaluated in the thalamus using also image analysis. Parvalbumin immunostaining in reticular nucleus neurons and in the dorsal thalamus neuropil, and the number of parvalbumin-positive and GABAergic cells in the laterodorsal and anterodorsal nuclei, exhibited an increase with respect to controls. Calbindin immunostaining was also enhanced, whereas calretinin immunostaining was mostly reduced, but was preserved in midline neurons. The findings show, after an acute seizure induced in an animal model of anti-convulsant mechanisms, regional long-term neurochemical alterations that could reflect functional changes in inhibitory and excitatory thalamic neurons.

The suprachiasmatic nucleus (SCN) projections to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-β subunit (CTb) were made in 12 different thalamic sites. These included individual midline thalamic nuclei (anterior, middle, and posterior portions of the paraventricular thalamic nucleus (PVT), intermediodorsal, paratenial, rhomboid, or reuniens nuclei) and intralaminar thalamic nuclei (lateral parafascicular, central lateral, or central medial nuclei) as well as the mediodorsal and anteroventral thalamic nuclei. After 10–14 days survival, the brains from these animals were processed histochemically and the distribution of retrogradely-labeled neurons was mapped throughout the rostralcaudal extent of the SCN. Within this collective group of midline and intralaminar thalamic nuclei, the only region innervated by the SCN was the PVT. Approximately 80% of this projection arose from the dorsomedial SCN, and the remaining projection originated from the ventrolateral SCN which targeted mainly the anterior division of the PVT. Virtually no SCN neurons were labeled after CTb injections centered in any of the other midline thalamic nuclei, which includes the intermediodorsal, mediodorsal, paratenial, rhomboid, or reuniens thalamic nuclei. Similarly, no evidence for a SCN projection to the intralaminar thalamic nuclei was found. The discussion focuses on the role of SCN → PVT pathway in modulating cerebral cortical functions.

AMPA receptors mediate fast synaptic transmission at collateral synapses of corticothalamic and thalamocortical axons in the thalamic reticular nucleus (RTN). These synapses are important in generating synchrony in the thalamocortical network. Whole cell recording in the mouse thalamocortical slice preparation was combined with high-resolution immunoelectron microscopy to characterize AMPA-mediated conductances at the two synapses and to correlate these with differential expression of GluR3 and GluR4 subunits. Thalamocortical collateral (TC) synapses had larger mean EPSC amplitudes (1914 ± 1814pS) than corticothalamic (CT) synapses (400 ± 257 pS), and rise and decay times of TC EPSCs were faster and less variable than CT EPSCs, probably reflecting proximal and dispersed locations of TC and CT terminals, respectively, on RTN cells. In situ hybridization and immunocytochemical studies revealed that GluRl and GluR2 subunits are not expressed in the RTN and GluR4 subunits are expressed at higher levels than GluR3 subunits. Immunoelectron microscopy revealed gold particles representing GluR3 or GluR4 subunits concentrated at single postsynaptic densities (PSD) characteristic of CT synapses and at the two to seven split PSD segments characteristic of TC synapses. At CT synapses the number and density of GluR4 particles were 2.5 times greater than GluR3 particles. At the larger TC synapses, the number of GluR3 particles exceeded that of GluR4 particles but density of GluR4 particles was lower than at CT synapses while density of GluR3 particles was similar. Despite enrichment of GluR4 subunits at CT synapses, larger conductances prevailed at thalamocortical collateral synapses, probably reflecting both larger overall numbers of AMPA receptors and a greater number of release sites represented by the split PSDs. Variability in amplitudes of TC EPSCs may reflect variability in the number of release sites; lower variability in CT EPSC amplitudes may reflect a more constant number of release sites.

Ca2+-dependent inactivation of Ca2+ channels represents a feedback mechanism to limit the influx of Ca2+ into cells. Since large Ca2+ transients are present in thalamocortical relay neurons and Ca2+-dependent mechanisms play a pivotal role for thalamic physiology, the existence of this inactivation mechanism and the involvement of different Ca2+ channel subtypes was investigated. The use of subtype-specific antibodies revealed the expression of α1A–α1E channel proteins on the cell body and proximal dendrites of acutely isolated cells from the rat dorsolateral geniculate nucleus (dLGN). In addition, subtype-specific channel blocking agents were used in whole cell patch clamp experiments: nifedipine (1–5 μM; L-type) blocked 35 ± 3%, ω-conotoxin GVIA (1 μM; N-type) blocked 27 ± 8%, and ω-conotoxin MVIIC (4 μM; P/Q-type) blocked 33 ± 5% of the total HVA Ca2+ current. The blocker-resistant current constituted about 12 ± 3% of the total Ca2+ current. The degree of Ca2+ current inactivation was assessed by using a two-pulse protocol. Under control conditions the post-pulse I/V was U-shaped with 35 ± 4% of the current undergoing inactivation. Inclusion of BAPTA to the internal pipette solution reduced the degree of inactivation to 15 ± 1%. When L- and P/Q-type current was blocked, the degree of inactivation was lowered to 20 ± 2 and 27 ± 3%, respectively. In the presence of ω-agatoxin TK (35 ± 6%) and ω-conotoxin GVIA (32 ± 1%) there was no change in inactivation. These data suggest that Ca2+-dependent inactivation is involved in the fine tuning of Ca2+ entry into relay neurons mediated by L- and Q-type channels locally operated by Ca2+ beneath the plasma membrane.

We examined the relationship between calbindin-D28k-defined subdivisions in the macaque inferior pulvinar and the patterns of afferent connections to cortical visual areas MT, V4 and V2. The subdivisions identified included the posterior (PIp), medial (PIm), central (PIc) and lateral (PIl) subdivisions. Projections to MT and V4 were largely segregated in the inferior pulvinar: projections to MT originated mainly from PIm, while projections to V4 originated mainly from PIl. In addition, weaker projections to MT were observed from PIp and PIc, and some projections from PIp to V4 were observed in one of two cases. Projections to V2 originated preferentially from PIl, with a lesser projection from PIc. No labeled cells were observed in PIm in five monkeys injected with various tracers into different regions of V2. Since most V2 injections were large enough to involve several neighboring stripe-like compartments, these findings suggest that PIm does not project to V2 compartments associated with neither dorsal nor ventral cortical processing streams. Cells projecting to V4 were not strictly segregated from those projecting to V2 in neither PIl nor PIc, suggesting that inferior pulvinar projections do not map the position of visual areas in the cortical mantle.

The effect of chronic high frequency deep brain stimulation (DBS) on rest tremor was investigated in subjects with Parkinson’s disease (PD). Eight PD subjects with high amplitude tremor (Group 1) and eight PD subjects with low amplitude tremor (Group 2, used as a reference group) were examined by a clinical neurologist and tested with a velocity laser to quantify time and frequency domain characteristics of tremor. Possible rebound effects in rest tremor when DBS was stopped for 60 min were also explored. Participants received DBS of the internal globus pallidus (GPi) (n = 7), the subthalamic nucleus (STN) (n = 6) or the ventrointermediate nucleus of the thalamus (Vim) (n = 3). Tremor was recorded with a velocity laser under two conditions of DBS (on-off) and two conditions of medication (L-Dopa on-off). Correlations between clinical and experimental results for tremor amplitude was 0.70 with no medication and no stimulation. In Group 1, DBS decreased tremor amplitude but also increased spectral concentration and median frequency significantly. Under medication, the changes in tremor with and without stimulation were not statistically significant (Group 1). When stimulation was stopped for 60 min, a rebound in tremor amplitude was observed and median frequency remained stable in Group 1. None of the comparisons examined produced significant effects in Group 2. Taken together, these results suggest that beyond its effect on tremor amplitude DBS acted also on tremor frequency and did not modify tremor characteristics in subjects with low amplitude tremor.

In a systematic study of thalamocortical relay neuron responses to sinusoidal current injection [J. Neurophysiol. 83 (1), 588], we found that the Fourier fundamental of tonic responses was regularly phase advanced during low temporal frequency stimulation (1/10 cycle at 0.1 Hz). We hypothesized that such phase advances of the Fourier fundamental response were due to a slow spike-frequency adaptation. Here we measure the time-dependence of the instantaneous firing rate during a current pulse protocol, confirm the presence of a slow spike-frequency adaptation, and quantify the adaptation time constant (0.6–2.0 s) and percentage adaptation of spike rate (40–60%). In light of these results, we augment a previously reported minimal integrate-and-fire-or-burst (IFB) neuron model with an adaptation current. When the parameters for this current are fit using a quantitative theory of spike-frequency adaptation [J. Neurophysiol. 79, 1549], the IFB model reproduces the experimentally observed phase advance of the Fourier fundamental response during sinusoidal current injection. Using fast-slow variable analysis, we develop a firing-rate reduction of the IFB model and perform parameter studies to investigate the dependence of the Fourier fundamental response (amplitude and phase) on the maximum conductance and recovery time constant for the adaptation current. Analytical calculations clarify the relationship between dc and ac measures of the suppression of response due to spike-frequency adaptation, show how the latter depends on stimulation frequency, and confirm the adaptation-induced phase advance of the Fourier fundamental observed in both experiment and simulation.

Voltage-activated calcium channels in thalamic neurons are considered important elements in the generation of thalamocortical burst firing during periods of electroencephalographic synchronization. A potent counterpart of calcium-mediated depolarization may reside in the activation of calcium-dependent potassium conductances. In the present study, thalamocortical relay cells that were acutely disso-ciated from the rat ventrobasal thalamic complex (VB) were studied using whole-cell patch-clamp techniques. The calcium-dependent potassium-current (IK(Ca)) was evident as a slowly activating component of outward current sensitive to the calcium ions (Ca2+)-channel blocker methoxyverapamil (10 μM) and to substitution of external calcium by manganese. The IK(Ca) was blocked by tetraethylam-monium chloride (1 mM) and iberiotoxin (100 nM), but not apamin (1 μM). In addition, isolated VB neurons were immunopositive to anti-α(913–926) antibody, a sequence-directed antibody to the a-subunit of “big” Ca2+-dependent K+-channel (BKCa) channels. Activators of the adenylyl cyclase cyclic adenosine monophosphate (cAMP) system, such as forskolin (20 μM), dibutyryl-cAMP (10 mM) and 3-isobutyl-1 -methylxanthine (500 μM), selectively and reversibly suppressed IK(Ca). These results suggest that a rise in intracellular cAMP level leads to a decrease in a calcium-dependent potassium conductance presumably mediated via BKCa type channels, thereby providing an additional mechanism by which neurotransmitter systems are able to control electrogenic activity in thalamocortical neurons and circuits during various states of electroencephalographic synchronization and de-synchronization.

An atlas of serial sections stained alternately for one of the three calcium-binding proteins, calbindin, calretinin or parvalbumin, or for markers that demarcate borders of thalamic nuclei in and around the posterior pole of the ventral posterior thalamic nucleus of a macaque monkey is presented. The concentrated focal zone of calbindin-immunoreactive fiber ramifications considered by others to form a specific pain and temperature relay nucleus is shown to be located entirely within the confines of the ventral posterior medial (VPM) nucleus. It contains a large population of calbindin-immunoreactive cells and overlaps a region of dense cell and fiber immunoreactivity for parvalbumin. In other parts of the ventral posterior complex, calbindin and parvalbumin immunoreactivity is complementary rather than co-extensive. It is unlikely that the zone of intense calbindin immunoreactivity in VPM forms the only thalamic relay for noxious thermal and mechanical inputs to the cerebral cortex.

Intracellular recordings from thalamocortical (TC) neurons in the ventrolateral (VL) nucleus as well as paired intracellular recordings from TC-VL neurons and area 4 cortical neurons under ketamine-xylazine anesthesia were performed to study changes in hyperpolarization-rebound sequences evoked by successive stimuli to the dorsal thalamus at different frequencies and the impact of these changes at the cortical level. The cellular mechanisms of such changes in synaptic networks connecting TC with cortical neurons are relevant for short-term plasticity during low-frequency oscillatory activities. The progressive decrease in hyperpolarization of TC cells in response to single thalamic stimulus above a certain frequency (generally >1 Hz) and to pulse-trains at 10 Hz was mainly due to synaptic factors and not to mechanisms intrinsic to TC cells, as revealed by comparing responses evoked by synaptic volleys to those elicited by hyperpolarizing current pulses mimicking the synaptically evoked hyperpolarization-rebound sequence. The decreased hyperpolarization to repetitive synaptic volleys, leading to a decreased number of action potentials in the post-inhibitory spike-burst, had an impact on cortical activities, being matched by a decreased rebound depolarization of cortical cell during repetitive augmenting responses. The alterations in hyperpolarization-rebound sequences upon repetitive stimulation, probably resulting from the decreased efficacy of connections between thalamic reticular (RE) neurons to TC connections, results in the dampening of activities sustaining normal, and possibly paroxysmal, oscillations in the TC network. Our results suggest that this phenomenon should be taken into account when analyzing complex activities, such as physiological and pathological oscillations.

GABA-ergic thalamic reticular neurons function generically or singularly in a state-dependent manner: during quiet sleep they synchronously and rhythmically inhibit thalamocortical neurons (TCNs) via bursts, thereby eliciting the low-threshold Ca2+ potentials in TCNs that are crucial to oscillatory network behavior in the thalamo-reticulo-cortical system; during wakefulness they shape the flux of ascending sensory information by inhibiting TCNs with asynchronous and arrhythmic single-spikes. To investigate how the reticulo-thalamic synapses, which occur throughout TCN dendrites, are able to effect such disparate functions, we have: (1) used a 1416 compartment model of a 3D reconstructed TCN; (2) triggered dendritic miniature (TTX-independent) and unitary (single-afferent) conductance-based synaptic events, and (3) recorded axial currents and voltage transients in all 1416 compartments simultaneously. For synapses at all dendritic locations, more than 79% of the charge transfer reached the soma, where it dispersed into other dendritic trees to return to the extracellular space. In accord, dendritic synapses in 80% of the arbor induced voltage responses that were severely attenuated at the soma (>75% loss). Spatio-temporal aspects of distributed postsynaptic responses were examined as well. Except for synapses in the 13 most proximal compartments, the amplitude and phase of the voltage responses degraded rapidly within a focal region that did not extend beyond the host tree, and was limited most often to a subtree. The bulk response (outside the focal region) was highly synchronous and uniform. Interestingly, there were not 1403 different focal regions, but only 20, each clearly distinct from the rest and sharply delineated. Structural attributes of the arbor determined their boundaries. Boundaries were invariant when the analysis was repeated on rescaled versions (length, diameter) of the reconstructed arbor. Unitary events also induced focal/bulk structures for both burst and single-spike triggers – paradigms that correspond to single-afferent drives during quiet sleep and arousal, respectively. Such qualities differ dramatically from previously proposed motifs of dendritic clustering, each of which carried nonlinear sensitivities to parameter values. We propose that dendritic clustering underlies the role of reticulo-thalamic synapses in the early processing of ascending sensory information and that bulk responses contribute robustness to the induction and maintenance oscillations in the thalamo-reticulo-cortical network.