The Role of Layer 6 Corticothalamic Circuits in Vision: Plasticity, Sensory Processing, and Behavior.

Cerebellar-responsive neurons in the thalamic ventroanterior-ventrolateral complex of rats: In vivo electrophysiology

Parvalbumin deficiency affects burst discharges but not network properties of the RTN.

1. Intracellular responses to stimulation of the cerebral cortex (Cx) and cerebellum were analyzed in thalamocortical neurons (TCNs) in the ventroanterior-ventrolateral (VA-VL) complex of the thalamus and neurons in the thalamic reticular nuclei (RNs) of anesthetized cats, and the contribution of reticular nucleus neurons (RNNs) and thalamic interneurons (TINs) to cerebral and cerebellar inhibition of TCNs was determined. 2. Single TCNs projecting to area 4 or 6 received convergent monosynaptic excitatory and disynaptic inhibitory inputs from both the dentate nucleus (DN) and the interpositus nucleus (IN). These TCNs also received monosynaptic excitatory postsynaptic potentials (EPSPs) and disynaptic inhibitory postsynaptic potentials (IPSPs) from the pericruciate cortex (areas 4 and 6). Each TCN received the strongest excitatory and inhibitory inputs from the cortical area to which that TCN projected, and weaker inhibitory inputs from adjacent cortical areas. 3. RNNs were identified morphologically by intracellular injection of horseradish peroxidase (HRP). Stimulation of the brachium conjunctivum (BC) evoked disynaptic EPSPs with a long decay phase in RNNs in the anterior ventrolateral part of the RN. Single RNNs received convergent disynaptic excitatory inputs from both the DNA and the IN. Stimulation of the Cx produced monosynaptic long-lasting EPSPs with two different latencies in these RNNs: early EPSPs with latencies of 0.9-2.1 ms and late EPSPs with latencies of 1.8-3.5 ms. Collision experiments with BC- and Cx-evoked EPSPs in RNNs indicated that BC-evoked disynaptic EPSPs and Cx-evoked early EPSPs were produced by axon collaterals of TCNs to RNNs. The latencies of the Cx-evoked late EPSPs in RNNs were almost identical to those of Cx-evoked monosynaptic EPSPs in TCNs, indicating that corticothalamic neurons (CTNs) exert monosynaptic excitatory effects on RNNs and TCNs. 4. Stimulation of the Cx produced IPSPs in TCNs with short latencies of 1.8-2.7 ms and longer latencies of > or = 2.8 ms. The Cx-evoked early IPSPs with latencies of 1.8-2.7 ms were mediated by RNNs. The origin of Cx-evoked late IPSPs with latencies of > or = 2.8 ms in TCNs was twofold, Cx-induced early IPSPs in TCNs were facilitated by conditioning cortical stimulation that induced late IPSPs in the TCNs. The same conditioning cortical stimulation also facilitated BC-evoked disynaptic IPSPs. The time course of this facilitatation indicated that CTNs produce long-lasting excitation in TINs. These results indicated that Cx-evoked IPSPs with latencies of > 2.7 ms were mediated at least in part by RNNs and inhibitory TINs in the VA-VL complex.(ABSTRACT TRUNCATED AT 400 WORDS)

The functional states of the thalamus and the associated neuronal interplay.

Cognitive and Perceptual Functions of the Visual Thalamus

Control of thalamic transmission by corticofugal and ascending reticular pathways in the visual system.

The thalamic reticular nucleus (TRN) occupies a highly strategic position to modulate sensory processing in the thalamocortical loop circuitries. It has been shown that TRN visual cells projecting to first- and higher-order thalamic nuclei have distinct levels of burst spiking, suggesting the possibility that the TRN exerts differential influences on information processing in first- and higher-order thalamic nuclei that compose the lemniscal and non-lemniscal sensory systems, respectively. To determine whether this possibility could extend across sensory modalities, the present study examined activities of TRN auditory cells projecting to the ventral and dorsal divisions (first- and higher-order auditory thalamic nuclei) of the medial geniculate nucleus (TRN-MGV and TRN-MGD cells) in anesthetized rats, using juxta-cellular recording and labeling techniques. Burst spiking of TRN-MGV cells consisted of larger numbers of spikes with shorter inter-spike intervals as compared with that of TRN-MGD cells in auditory response evoked by noise burst stimuli. Similar distinctions, although not statistically significant, were observed in spontaneous activity. Furthermore, the features of burst spiking varied in association with the topographies of cell body and terminal field locations. These features of burst spiking are similar to those observed in the two types of TRN visual cells. First- and higher-order thalamic nuclei are known to have distinct levels of burst spiking across sensory modalities. Taken together, it is suggested that the distinctions in burst spiking in the TRN, in conjunction with those in thalamic nuclei, could constitute distinct circuitries for lemniscal and non-lemniscal sensory processing in the thalamocortical loop.

Subtype-specific alterations in first- and higher-order thalamic reticular neurons in the Shank3 mutant mouse model of autism.

The thalamic reticular nucleus is a thin layer of GABAergic cells located between the external medullary lamina and the internal capsule surrounding the rostolateral surface of the thalamus. It has functionally distinct afferent and efferent connections with thalamic nuclei, the neocortex, the basal forebrain and the brainstem. Parvalbumin is a calcium-binding protein, which is regarded to be a marker for GABAergic neurons. The thalamic reticular neurons are GABAergic, and parvalbumin is always colocalized with GABA in these cells. We have demonstrated the parvalbumin immunoreactivity in the thalamic reticular nucleus at different stages of postnatal development of rats, as well at 1-year-old rats. It was established that the maturation of immunoposive patterns varies in different parts of the nucleus. The intensity of immunostaining decreases with age.

Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats

Most dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a 'canonical' circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6-1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex.

The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development.Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2–4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2–4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4–6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry.

The activity of the GABAergic neurons of the thalamic reticular nucleus (TRN) has long been known to play important roles in modulating the flow of information through the thalamus and in generating changes in thalamic activity during transitions from wakefulness to sleep. Recently, technological advances have considerably expanded our understanding of the functional organization of TRN. These have identified an impressive array of functionally distinct subnetworks in TRN that participate in sensory, motor, and/or cognitive processes through their different functional connections with thalamic projection neurons. Accordingly, “first order” projection neurons receive “driver” inputs from subcortical sources and are usually connected to a densely distributed TRN subnetwork composed of multiple elongated neural clusters that are topographically organized and incorporate spatially corresponding electrically connected neurons—first order projection neurons are also connected to TRN subnetworks exhibiting different state-dependent activity profiles. “Higher order” projection neurons receive driver inputs from cortical layer 5 and are mainly connected to a densely distributed TRN subnetwork composed of multiple broad neural clusters that are non-topographically organized and incorporate spatially corresponding electrically connected neurons. And projection neurons receiving “driver-like” inputs from the superior colliculus or basal ganglia are connected to TRN subnetworks composed of either elongated or broad neural clusters. Furthermore, TRN subnetworks that mediate interactions among neurons within groups of thalamic nuclei are connected to all three types of thalamic projection neurons. In addition, several TRN subnetworks mediate various bottom-up, top-down, and internuclear attentional processes: some bottom-up and top-down attentional mechanisms are specifically related to first order projection neurons whereas internuclear attentional mechanisms engage all three types of projection neurons. The TRN subnetworks formed by elongated and broad neural clusters may act as templates to guide the operations of the TRN subnetworks related to attentional processes. In this review article, the evidence revealing the functional TRN subnetworks will be evaluated and will be discussed in relation to the functions of the various sensory and motor thalamic nuclei with which these subnetworks are connected.

The thalamic reticular nucleus (TRN) provides inhibitory innervation to most thalamic relay nuclei and receives excitatory innervation from both cortical and thalamic neurons. Ultimately, information transfer through the thalamus to the neocortex is strongly influenced by TRN. In addition, the reciprocal synaptic connectivity between TRN with associated thalamic relay nuclei is critical in generating intrathalamic rhythmic activities that occur during certain arousal states and pathophysiological conditions. Despite evidence suggesting morphological heterogeneity amongst TRN neurons, the heterogeneity of intrinsic properties of TRN neurons has not been systematically examined. One key characteristic of virtually all thalamic neurons is the ability to produce action potentials in two distinct modes: burst and tonic. In this study, we have examined the prevalence of burst discharge within TRN neurons. Our intracellular recordings revealed that TRN neurons can be differentiated by their action potential discharge modes. The majority of neurons in the dorsal TRN (56%) lack burst discharge, and the remaining neurons (35%) show an atypical burst that consists of an initial action potential followed by small amplitude, long duration depolarizations. In contrast, most neurons in ventral TRN (82%) display a stereotypical burst discharge consisting of a transient, high frequency discharge of multiple action potentials. TRN neurons that lack burst discharge typically did not produce low threshold calcium spikes or produced a significantly reduced transient depolarization. Our findings clearly indicate that TRN neurons can be differentiated by differences in their spike discharge properties and these subtypes are not uniformly distributed within TRN. The functional consequences of such intrinsic differences may play an important role in modality-specific thalamocortical information transfer as well as overall circuit level activities.

Aligning one’s sights: The pulvinar provides context for visual information processing