Thalamic Relay Cells Research Articles

Prefrontal cortical modulation of information flow in a large-scale model of the cortico-thalamic circuit

While generating the stream of consciousness and driving our actions in the world the brain largely relies on implicit forms of information processing. Conscious and unconscious factors are closely coupled and can be seen as complementary since unconscious processing can be sensitive to regularities within signals prior to conscious awareness, suggesting that the content of consciousness can be biased by unconscious factors. In the context of the Distributed Adaptive Control (DAC) theory of the mind, brain and body nexus [1], we previously developed different probabilistic models of perception and attention that include bottom-up and top-down processes in defining an anticipatory gate to restrict the prediction of future incoming stimuli [2]. These results suggest that unconscious information presented at the border of this anticipatory gate could lead to a re-organization of perception and cognition by modifying sensory expectations. A plausible neuronal substrate for this top-down shaping mechanism has been identified in the circuitry including prefrontal cortical areas and the thalamus by mediation of the inhibitory thalamic reticular nucleus (TRN) interposed between the thalamus and the cortex. TRN is uniquely innervated by prefrontal projections, both by large ('driving') and small ('modulatory') synaptic boutons, that extends into the sensory sectors of the nuclei [3] indicating a possible role in the regulation of the sensory information flow from the thalamus to the cortex. Building on an initial large scale model of thalamo-cortical dysrhythmia [4], the present study describes a spiking model of the cortico thalamic loops that aims at explaining how concurrent sensory inputs can be effectively gated by the activation of prefrontal projections to the TRN. The model consists of a network of pyramidal cells, interneurons, thalamic reticular and thalamocortical relay cells and includes driving and modulatory connections from the prefrontal areas to the TR nuclei. We show that inputs from the prefrontal cortex (and its homologous thalamic area) can selectively favor one of two incoming thalamic stimuli by activating neighboring TRN neurons and thus inhibiting the thalamic relay cells activated by the concurrent stimulus. The stimulus is then not sufficiently strong to be transmitted to the cortical areas. PFC top-down expectations can thus act as a filter on the thalamus (by the mediation of the RTN) to suppress irrelevant signals and maintain a coherent internal state. As a follow up we want to test the prediction that the same mechanism can drive to conscious percepts following strong expectations even in the absence of external stimuli.

GABAergic Synaptic Transmission Triggers Action Potentials in Thalamic Reticular Nucleus Neurons

GABAergic neurons in the thalamic reticular nucleus (TRN) form powerful inhibitory connections with several dorsal thalamic nuclei, thereby controlling attention, sensory processing, and synchronous oscillations in the thalamocortical system. TRN neurons are interconnected by a network of GABAergic synapses, but their properties and their role in shaping TRN neuronal activity are not well understood. Using recording techniques aimed to minimize changes in the intracellular milieu, we show that synaptic GABA(A) receptor activation triggers postsynaptic depolarizations in mouse TRN neurons. Immunohistochemical data indicate that TRN neurons express very low levels of the Cl(-) transporter KCC2. In agreement, perforated-patch recordings show that intracellular Cl(-) levels are high in TRN neurons, resulting in a Cl(-) reversal potential (E(Cl)) significantly depolarized from rest. Additionally, we find that GABA(A) receptor-evoked depolarizations are amplified by the activation of postsynaptic T-type Ca(2+) channels, leading to dendritic Ca(2+) increases and the generation of burst firing in TRN neurons. In turn, GABA-evoked burst firing results in delayed and long-lasting feedforward inhibition in thalamic relay cells. Our results show that GABA-evoked depolarizations can interact with T-type Ca(2+) channels to powerfully control spike generation in TRN neurons.

Feedforward Origins of Response Variability Underlying Contrast Invariant Orientation Tuning in Cat Visual Cortex

Contrast invariant orientation tuning in simple cells of the visual cortex depends critically on contrast dependent trial-to-trial variability in their membrane potential responses. This observation raises the question of whether this variability originates from within the cortical circuit or the feedforward inputs from the lateral geniculate nucleus (LGN). To distinguish between these two sources of variability, we first measured membrane potential responses while inactivating the surrounding cortex, and found that response variability was nearly unaffected. We then studied variability in the LGN, including contrast dependence, and the trial-to-trial correlation in responses between nearby neurons. Variability decreased significantly with contrast, whereas correlation changed little. When these experimentally measured parameters of variability were applied to a feedforward model of simple cells that included realistic mechanisms of synaptic integration, contrast-dependent, orientation independent variability emerged in the membrane potential responses. Analogous mechanisms might contribute to the stimulus dependence and propagation of variability throughout the neocortex.

Setting the Time Course of Inhibitory Synaptic Currents by Mixing Multiple GABAAReceptor α Subunit Isoforms

The kinetics of IPSCs influence many neuronal processes, such as the frequencies of oscillations and the duration of shunting inhibition. The subunit composition of recombinant GABA(A) receptors (GABA(A)Rs) strongly affects the deactivation kinetics of GABA-evoked currents. However, for GABAergic synapses, the relationship between subunit composition and IPSC decay is less clear. Here we addressed this by combining whole-cell recordings of miniature IPSCs (mIPSCs) and quantitative immunolocalization of synaptic GABA(A)R subunits. In cerebellar stellate, thalamic relay, and main olfactory bulb (MOB) deep short-axon cells of Wistar rats, the only synaptic α subunit was α1, and zolpidem-sensitive mIPSCs had weighted decay time constants (τ(w)) of 4-6 ms. Nucleus reticularis thalami neurons expressed only α3 as the synaptic α subunit and exhibited slow (τ(w) = 28 ms), zolpidem-insensitive mIPSCs. By contrast, MOB external tufted cells contained two α subunit types (α1 and α3) at their synapses. Quantitative analysis of multiple immunolabeled images revealed small within-cell, but large between-cell, variability in synaptic α1/α3 ratios. This corresponded to large cell-to-cell variability in the decay (τ(w) = 3-30 ms) and zolpidem sensitivity of mIPSCs. Currents evoked by rapid application of GABA to patches excised from HEK cells expressing different mixtures of α1 and α3 subunits displayed highly variable deactivation times that correlated with the α1/α3 cDNA ratio. Our results demonstrate that diversity in the decay of IPSCs can be generated by varying the expression of different GABA(A)R subunits that alone confer different decay kinetics, allowing the time course of inhibition to be tuned to individual cellular requirements.

State-Dependent Modulation of Gap Junction Signaling by the Persistent Sodium Current

Thalamic neurons fluctuate between two states: a hyperpolarized state associated with burst firing and sleep spindles, and a depolarized state associated with tonic firing and rapid, reliable information transmission between the sensory periphery and cortex. The thalamic reticular nucleus (TRN) plays a central role in thalamocortical processing by providing feed-forward and feedback inhibition to thalamic relay cells; TRN cells participate in the generation of sleep spindles, and have been suggested to focus the neural “searchlight” of attention. The mechanisms underlying synchrony in the TRN during different behavioral states are largely unknown. TRN cells are densely interconnected by electrical synapses. Here we show that activation of the persistent sodium current (INaP) by depolarization causes up to fourfold changes in electrical synaptic efficacy between TRN neurons. We further show that amplification of electrical synaptic responses strongly enhances tonic spike synchrony but, surprisingly, does not affect burst coordination. We use a Hodgkin–Huxley model to gain insight into the differences between the effects of burstlets, spikelets, and amplification on burst and spike times.

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Compared to the developing visual system, where neuronal plasticity has been well characterized at multiple levels, little is known about plasticity in the adult, particularly within subcortical structures. We made intraocular injections of 2-amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On-center retinal ganglion cells and examined the consequences on visual responses in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current views of retinogeniculate organization, which hold that On-center LGN neurons should become silent with APB, we find that ∼50% of On-center neurons rapidly develop Off-center responses. The time course of these emergent responses and the actions of APB in the retina indicate the plasticity occurs within the LGN. These results suggest there is greater divergence of retinogeniculate connections than previously recognized and that functionally silent, nonspecific retinal inputs can serve as a substrate for rapid plasticity in the adult.

Neural Feedback for Instantaneous Spatiotemporal Modulation of Afferent Pathways in Bi-Directional Brain–Machine Interfaces

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

WNK2 Kinase Is a Novel Regulator of Essential Neuronal Cation-Chloride Cotransporters

NKCC1 and KCC2, related cation-chloride cotransporters (CCC), regulate cell volume and γ-aminobutyric acid (GABA)-ergic neurotranmission by modulating the intracellular concentration of chloride [Cl−]. These CCCs are oppositely regulated by serine-threonine phosphorylation, which activates NKCC1 but inhibits KCC2. The kinase(s) that performs this function in the nervous system are not known with certainty. WNK1 and WNK4, members of the WNK (with no lysine [K]) kinase family, either directly or via the downstream SPAK/OSR1 Ste20-type kinases, regulate the furosemide-sensitive NKCC2 and the thiazide-sensitive NCC, kidney-specific CCCs. What role the novel WNK2 kinase plays in this regulatory cascade, if any, is unknown. Here, we show that WNK2, unlike other WNKs, is not expressed in kidney; rather, it is a neuron-enriched kinase primarily expressed in neocortical pyramidal cells, thalamic relay cells, and cerebellar granule and Purkinje cells in both the developing and adult brain. Bumetanide-sensitive and Cl−-dependent 86Rb+ uptake assays in Xenopus laevis oocytes revealed that WNK2 promotes Cl− accumulation by reciprocally activating NKCC1 and inhibiting KCC2 in a kinase-dependent manner, effectively bypassing normal tonicity requirements for cotransporter regulation. TiO2 enrichment and tandem mass spectrometry studies demonstrate WNK2 forms a protein complex in the mammalian brain with SPAK, a known phosphoregulator of NKCC1. In this complex, SPAK is phosphorylated at Ser-383, a consensus WNK recognition site. These findings suggest a role for WNK2 in the regulation of CCCs in the mammalian brain, with implications for both cell volume regulation and/or GABAergic signaling.

Cortical modulation of neuronal activity in the cat's lateral geniculate and perigeniculate nuclei: a modeling study

The role of cortical feedback in thalamo-cortical processing loop have been extensively investigated over the last decades. In general, these studies focused on cortical feedback exerted over lateral geniculate nucleus (LGN) principal cells, only in several cases the effects of cortical inactivation were investigated simultaneously in both thalamic relay cells and perigeniculate nucleus (PGN) inhibitory neurons. In the previous study [1] we showed in the cat that cessation of cortical input by cooling of visual cortex (areas 17 and 18) decreased spontaneous activity of LGN relay cells and increased spontaneous activity of PGN neurons. In contrast, visually evoked responses of most PGN neurons and LGN principal cells both decreased. To identify network mechanisms underlying such functional changes we conducted a modelling study in NEURON on several networks of point neurons with varied model parameters, such as membrane properties, synaptic weights and axonal delays. We considered five network topologies of the retino-geniculo-cortical pathway [2-6]. All models were robust against changes of axonal delays except for delay between LGN feed-forward interneuron and principal cell when this connection was present. In all such cases the models were found to be very sensitive to this delay. To reproduce the experimental results [1] the models required: 1) reciprocally connected PGN cells, connection present only in two model variants [2,3], and 2) slow decay of intracellular calcium. We found model [2] most consistent with known physiology and anatomy of the cat. Table ​Table1.1. Figure ​Figure11. Table 1 Mean spontaneous activity (spikes/s) for tested models (mean of 30 repetitions) and t-test P values. Figure 1 The model network of the thalamo-cortical loop following [2]. The model in [3] does not include LGN feedforward interneuron. Both variants reproduced experimental results [1]. White circles – relay cells, black – inhibitory neurons.

Target-Dependent Control of Synaptic Inhibition by Endocannabinoids in the Thalamus

Inhibitory neurons in the thalamic reticular nucleus (TRN) play a critical role in controlling information transfer between thalamus and neocortex. GABAergic synapses formed by TRN neurons contact both thalamic relay cells and neurons within TRN. These two types of synapses are thought to have distinct roles for the generation of thalamic network activity, but their selective regulation is poorly understood. In many areas throughout the brain, retrograde signaling mediated by endocannabinoids acts to dynamically regulate synaptic strength over both short and long time scales. However, retrograde signaling has never been demonstrated in the thalamus. Here, we show that depolarization-induced suppression of inhibition (DSI) is prominent at inhibitory synapses interconnecting TRN neurons. DSI is completely abolished in the presence of a cannabinoid receptor 1 (CB1R) antagonist and in mice lacking CB1Rs. DSI is prevented by DAG lipase inhibitors and prolonged by blocking the 2-arachidonoylglycerol (2-AG) degradation enzyme monoacylglycerol lipase, indicating that it is mediated by the release of 2-AG from TRN neurons. By contrast, DSI is not observed at TRN synapses targeting thalamic relay neurons. A combination of pharmacological and immunohistochemical data indicate that the differences in endocannabinoid signaling at the two synapses are mediated by a synapse-specific targeting of CB1Rs, as well as differences in endocannabinoid release between the two target neurons. Together, our results show that endocannabinoids control transmitter release at specific thalamic synapses, and could dynamically regulate sensory information processing and thalamus-mediated synchronous oscillations.

Functional Organization of the Thalamic Input to the Thalamic Reticular Nucleus

Most axons connecting the thalamus and cortex in both directions pass through the thalamic reticular nucleus (TRN), a thin layer of GABAergic cells adjacent to the thalamus, and innervate neurons there. The TRN, therefore, is in a strategic location to regulate thalamocortical communication. We recorded neurons of the somatosensory region of the TRN in a thalamocortical slice preparation and studied the spatial organization of their thalamic input using laser scanning photostimulation. We show that the thalamoreticular pathway is organized topographically for most neurons. The somatosensory region of the TRN can be organized into three tiers. From the inner (thalamoreticular) border to the outer, in a manner roughly reciprocal to the reticulothalamic pathway, each of these tiers receives its input from one of the somatosensory relays of the thalamus--the posterior medial, ventroposterior medial, and ventroposterior lateral nuclei. What is surprising is that approximately a quarter of the recorded neurons received input from multiple thalamic regions usually located in different nuclei. These neurons distribute evenly throughout the thickness of the TRN. Our results, therefore, suggest that there exist a subpopulation of TRN neurons that receive convergent inputs from multiple thalamic sources and engage in more complex patterns of inhibition of relay cells. We propose these neurons enable the TRN to act as an externally driven "searchlight" that integrates cortical and subcortical inputs and then inhibits or disinhibits specific thalamic relay cells, so that appropriate information can get through the thalamus to the cortex.

Receptor saturation controls short-term synaptic plasticity at corticothalamic synapses

Glutamatergic synapses of layer 6 corticothalamic (CT) neurons form a major excitatory input onto thalamic relay cells, allowing neocortex to continuously control sensory information processing in thalamic circuits. CT synapses display both short- and long-term forms of use-dependent synaptic enhancement, mediated at least in part by increases in the probability of transmitter release. At some synapses, such increases in release probability are accompanied by a higher degree of multivesicular release (MVR) and larger glutamate transients at individual release sites, resulting in the saturation of postsynaptic receptors. The extent to which MVR and postsynaptic saturation interact and control short-term plasticity at CT synapses is not known. Here we examined two distinct presynaptic forms of short-term enhancement, facilitation and augmentation, at CT synapses contacting relay neurons in the ventrobasal nucleus of the mouse thalamus. We found that, in the presence of the low-affinity antagonist γ-D-glutamylglycine, to relieve postsynaptic DL-α-amino-3-hydroxy-5-methylisox azole-propionic acid (AMPA) receptor saturation, the magnitude of facilitation and augmentation increased. Whereas receptor saturation was prominent for both AMPA and N-methyl-D-aspartate receptors, desensitization of AMPA receptors did not significantly alter short-term plasticity. Our results suggest that at CT synapses the activity-dependent increase in synaptic strength is controlled by postsynaptic receptor saturation.

Thalamic interneurons and relay cells use complementary synaptic mechanisms for visual processing

Synapses made by local interneurons dominate the thalamic circuits that process signals traveling from the eye downstream. The anatomical and physiological differences between interneurons and the (relay) cells that project to cortex are vast. To explore how these differences might influence visual processing, we made intracellular recordings from both classes of cells in vivo. Macroscopically, all receptive fields were similar, made of two concentrically arranged subregions in which dark and bright stimuli elicited responses of the reverse sign. Microscopically, however, the responses of the two types of cells had opposite profiles. Excitatory stimuli drove trains of single EPSPs in relay cells but graded depolarizations in interneurons. By contrast, suppressive stimuli evoked smooth hyperpolarizations in relay cells but unitary IPSPs in interneurons. Computational analyses suggested that these complementary patterns of response help preserve information encoded within the fine timing of retinal spikes and increase the amount of information transmitted to cortex.

Signalling properties of bursts and spikes in model thalamic relay cells

Signalling properties of bursts and spikes in model thalamic relay cells

Thalamocortical interactions in first- and higher order thalamic nuclei

Event Abstract Back to Event Thalamocortical interactions in first- and higher order thalamic nuclei Péter Barthó1*, István Ulbert2 and László Acsády1 1 Hungarian Academy of Sciences, Institute of Experimental Medicine, Hungary 2 Hungarian Academy of Sciences, Institute of Psychology, Hungary During natural sleep and anesthesia, neocortical activity is characterized by periods of synchronized activity alternating with periods of silence (up- and down-states). Despite being the most numerous input source and output target of the cortex, the relation of thalamus to synchronized cortical activity is not yet fully established. Thalamic nuclei differ in their connectivity; first order (FO) thalamic nuclei receive driving inputs from various subcortical centers whereas higher order (HO) nuclei are contacted by driving afferents arising from cortical layer V. Besides, all thalamic nuclei receive strong modulatory input from cortical layer VI. To investigate thalamocortical synchrony, we performed simultaneous multiple single-unit recordings in rats under urethane anesthesia in the somatosensory FO ventral postero-medial nucleus (VPM), the HO nucleus posterior (Po) and in the S1 cortex. The recordings were made using four-shank silicon probes, which could span different nuclei. The exact electrode position was determined by pre-labeling the probes with DiI. In Po, thalamic relay activity showed up-and down states, with majority of cells firing phase locked to cortical activity. In VPM, however, thalamic firing was weakly coupled to cortical up- and down states. Instead, the activity was dominated by local spindles, which were frequently restricted to one or two electrode shanks, and only occasionally spread to the neocortex. In the VPM another type of unit was also recorded with narrower spike waveforms, longer burst duration, and higher activity during spindles. These features indicate that they can potentially be the axon terminals of reticular thalamic neuron Relay cells and putative nRt terminals fired at different phases of spindle oscillations, with relay cells preceding nRt terminals. Our data demonstrate distinct population activity in first order, higher order and reticular thalamic nuclei. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Sensory and motor systems Citation: Barthó P, Ulbert I and Acsády L (2010). Thalamocortical interactions in first- and higher order thalamic nuclei. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00062 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 21 Apr 2010; Published Online: 21 Apr 2010. * Correspondence: Péter Barthó, Hungarian Academy of Sciences, Institute of Experimental Medicine, Budapest, Hungary, bartho@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Péter Barthó István Ulbert László Acsády Google Péter Barthó István Ulbert László Acsády Google Scholar Péter Barthó István Ulbert László Acsády PubMed Péter Barthó István Ulbert László Acsády Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Pathway-Specific Feedforward Circuits between Thalamus and Neocortex Revealed by Selective Optical Stimulation of Axons

Thalamocortical and corticothalamic pathways mediate bidirectional communication between the thalamus and neocortex. These pathways are entwined, making their study challenging. Here we used lentiviruses to express channelrhodopsin-2 (ChR2), a light-sensitive cation channel, in either thalamocortical or corticothalamic projection cells. Infection occurred only locally, but efferent axons and their terminals expressed ChR2 strongly, allowing selective optical activation of each pathway. Laser stimulation of ChR2-expressing thalamocortical axons/terminals evoked robust synaptic responses in cortical excitatory cells and fast-spiking (FS) inhibitory interneurons, but only weak responses in somatostatin-containing interneurons. Strong FS cell activation led to feedforward inhibition in all cortical neuron types, including FS cells. Corticothalamic stimulation excited thalamic relay cells and inhibitory neurons of the thalamic reticular nucleus (TRN). TRN activation triggered inhibition in relay cells but not in TRN neurons. Thus, a major difference between thalamocortical and corticothalamic processing was the extent to which feedforward inhibitory neurons were themselves engaged by feedforward inhibition.

Selective Targeting of the Dendrites of Corticothalamic Cells by Thalamic Afferents in Area 17 of the Cat

Pyramidal cells of layer 6 in cat visual cortex are the source of the corticothalamic projection, and their recurrent collaterals provide substantially more excitatory synapses in layer 4 than does the thalamic input. They have predominantly simple receptive fields and can be driven monosynaptically by electrically stimulating thalamic relay cells. Layer 6 cells could thus provide a significant disynaptic amplification of the thalamic input to layer 4, particularly since their synapses facilitate, unlike the thalamic afferents whose synapses depress. However, purely geometric considerations of the relation of their dendritic trees to the thalamic input indicate that they should form a far smaller number of synapses with thalamic afferents than do the simple cells of layer 4. We thus analyzed quantitatively the thalamic input to identified corticothalamic cells by labeling the thalamic afferents and corticothalamic cells in vivo. We made a correlated light and electron microscopic study of 73 "contacts" between thalamic afferents and five corticothalamic cells. The electron microscope revealed that only 24 of the contacts identified at light microscope level were indeed synapses and, contrary to geometric predictions, virtually all were located on spines on the basal dendrites. Our quantitative estimates indicate that the corticothalamic cells form even fewer synapses with the thalamic afferents than predicted by geometric considerations and only 1/10 as many as do the layer 4 simple cells. These data strongly suggest it is the collective computation of cortical neurons, not the monosynaptic thalamic input, that determines the output of the corticothalamic cells.

Stability of Electrical Coupling despite Massive Developmental Changes of Intrinsic Neuronal Physiology

Gap junctions mediate metabolic and electrical interactions between some cells of the CNS. For many types of neurons, gap junction-mediated electrical coupling is most prevalent during early development, then decreases sharply with maturation. However, neurons in the thalamic reticular nucleus (TRN), which exert powerful inhibitory control over thalamic relay cells, are electrically coupled in relatively mature animals. It is not known whether TRN cells or any neurons that are electrically coupled when mature are also coupled during early development. We used dual whole-cell recordings in mouse brain slices to study the postnatal development of electrical and chemical synapses that interconnect TRN neurons. Inhibitory chemical synapses were seen as early as postnatal day 4 but were infrequent at all ages, whereas TRN cells were extensively connected by electrical synapses from birth onward. Surprisingly, the functional strength of electrical coupling, assayed under steady-state conditions or during spiking, remained relatively constant as the brain matured despite dramatic concurrent changes of intrinsic membrane properties. Most notably, neuronal input resistances declined almost eightfold during the first two postnatal weeks, but there were offsetting increases in gap junctional conductances. This suggests that the size or number of gap junctions increase homeostatically to compensate for leakier nonjunctional membranes. Additionally, we found that the ability of electrical synapses to synchronize high frequency subthreshold signals improved as TRN cells matured. Our results demonstrate that certain central neurons may maintain or even increase their gap junctional communication as they mature.

Nonlinear Influence of T-Channels in anin silicoRelay Neuron

Thalamic relay cells express distinctive response modes based on the state of a low-threshold calcium channel (T-channel). When the channel is fully active (burst mode), the cell responds to inputs with a high-frequency burst of spikes; with the channel inactive ( tonic mode), the cell responds at a rate proportional to the input. Due to the T-channel's dynamics, we expect the cell's response to become more nonlinear as the channel becomes more active. To test this hypothesis, we study the response of an in silico relay cell to Poisson spike trains. We first validate our model cell by comparing its responses with in vitro responses. To characterize the model cell's nonlinearity, we calculate Poisson kernels, an approach akin to white noise analysis but using the randomness of Poisson input spikes instead of Gaussian white noise. We find that a relay cell with active T-channels requires at least a third-order system to achieve a characterization as good as a second-order system for a relay cell without T-channels.

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