Emerging views of corticothalamic function

Although it is now generally accepted that the thalamus is more than a simple relay of sensory signals to the cortex, we are just beginning to gain an understanding of how corticothalamic feedback influences sensory processing. Results from an increasing number of studies across sensory systems and different species reveal effects of feedback both on the receptive fields of thalamic neurons and on the transmission of sensory information between the thalamus and cortex. Importantly, these studies demonstrate that the cortico-thalamic projection cannot be viewed in isolation, but must be considered as an integral part of a thalamo-corticothalamic circuit which intimately interconnects the thalamus and cortex for sensory processing.     

The role of spike timing for thalamocortical processing

Although the response properties of sensory neurons in the thalamus and cerebral cortex have been studied for decades, relatively few studies have examined how sensory information is processed at thalamocortical synapses. Recent studies now show that the strength of thalamocortical connections is very dynamic and spike timing plays an important role in determining whether action potentials will be transferred from thalamus to cortex.     

Synchrony in sensation

How neurons encode information has been a hotly debated issue. Ultimately, any code must be relevant to the senders, receivers, and connections between them. This review focuses on the transmission of sensory information through the circuit linking thalamus and cortex, two distant brain regions. Strong feedforward inhibition in the thalamocortical circuit renders cortex highly sensitive to the thalamic synchrony evoked by a sensory stimulus. Neuromodulators and feedback connections may modulate the temporal sensitivity of such circuits and gate the propagation of synchrony into other layers and cortical areas. The prevalence of strong feedforward inhibitory circuits throughout the central nervous system suggests that synchrony codes and timing-sensitive circuits may be widespread, occurring well beyond sensory thalamus and cortex.     

Is the "nonspecific" thalamus still "nonspecific"?

The classical concept of "nonspecific" thalamus, as distinguished from the principal thalamic nuclei (i.e. the primary sensory, motor and limbic relays) is here briefly revisited in the light of anatomical investigations performed in the last decades, and primarily those based on tract tracing techniques. Altogether these data pointed out that the so-called "nonspecific" thalamus is composed by a heterogeneous collection of nuclear masses, which display not only species differences, but also marked internuclear variations in their cytological and neurochemical features, connections, areal and laminar distribution upon the cortex, and functional properties. Thus, the "nonspecific" thalamus exerts a modulatory role on cortical activity, chiefly regulated at the intrathalamic level by the interplay between the thalamic reticular nucleus and the interneurons and projection neurons of the dorsal thalamus. However, each of the components that have been traditionally considered as "nonspecific" also subserves selective roles in the transfer of different kinds of information from the thalamus to the cerebral cortex and basal ganglia.     

In vivo and in vitro patch-clamp recording analysis of the process of sensory transmission in the spinal cord and sensory cortex

Following the integration and modification of the sensory inputs in the spinal cord, the information is transmitted to the primary sensory cortex where the integrated information is further processed and perceived. Processing of the sensory information in the spinal cord has been intensively investigated. However, the mechanisms of how the inputs are processed in the cortex are still unclear. To know the correlation of the sensory processing in the dorsal horn and cortex, in vivo and in vitro patch-clamp recordings were made from rat dorsal horn and sensory cortex. Although dorsal horn neurons showed spontaneous and evoked EPSCs by noxious and non-noxious stimuli, most somatosensory neurons located at 100 to 1000 microm from the surface of the cortex exhibited an oscillatory activity and received synaptic inputs from non-noxious but not noxious receptors. These observations suggest that the synaptic responses in cortical neurons are processed in a more complex manner; and this may be due to the reciprocal synaptic connection between thalamus and cortex.     

Quantitative trait loci linked to thalamus and cortex gray matter volumes in BXD recombinant inbred mice

To investigate whether there are separate or shared genetic influences on the development of the thalamus and cerebral cortex, we identified quantitative trait loci (QTLs) for relevant structural volumes in BXD recombinant inbred (RI) strains of mice. In 34 BXD RI strains and two parental strains (C57BL/6J and DBA/2J), we measured the volumes of the entire thalamus and cortex gray matter using point counting and Cavalieri's rule. Heritability was calculated using analysis of variance (ANOVA), and QTL analysis was carried out using WebQTL (http://www.genenetwork.org). The heritability of thalamus volume was 36%, and three suggestive QTLs for thalamus volume were identified on chromosomes 10, 11 and 16. The heritability of cortical gray matter was 43%, and four suggestive QTLs for cortex gray matter volume were identified on chromosomes 2, 8, 16 and 19. The genetic correlation between thalamus and cortex gray matter volumes was 0.64. Also, a single QTL on chromosome 16 (D16Mit100) was identified for thalamus volume, cortex gray matter volume and Morris water maze search-time preference (r=0.71). These results suggest that there are separate and shared genetic influences on the development of the thalamus and cerebral cortex.     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

Predicting functional properties of visual cortex from an evolutionary scaling law

The number of neurons in the primary visual cortex (V1) is, across primate species, related to the number of neurons in the visual thalamus (the lateral geniculate nucleus [LGN]) by a power law with an exponent of 3/2. This evolutionary scaling law is explained by a simple relation according to which the fineness of resolution in cortex is related to the number of neurons in the area of cortex used to process the information from a single point of light (the point-spread area). The same theory provides a link between two functional properties of the visual cortex, the areal cortical magnification factor (ACMF) and the receptive field (RF) area.     

Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression

The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.     

Auditory processing across the sleep-wake cycle: simultaneous EEG and fMRI monitoring in humans

We combined fMRI and EEG recording to study the neurophysiological responses associated with auditory stimulation across the sleep-wake cycle. We found that presentation of auditory stimuli produces bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and nonrapid eye movement (NREM) sleep. However, the left parietal and, bilaterally, the prefrontal and cingulate cortices and the thalamus were less activated during NREM sleep compared to wakefulness. These areas may play a role in the further processing of sensory information required to achieve conscious perception during wakefulness. Finally, during NREM sleep, the left amygdala and the left prefrontal cortex were more activated by stimuli having special affective significance than by neutral stimuli. These data suggests that the sleeping brain can process auditory stimuli and detect meaningful events.     

THE EFFECTS OF PENTOBARBITONE-SODIUM ANAESTHESIA, SHOCK AVOIDANCE CONDITIONING AND ELECTRICAL SHOCK ON ACETYLCHOLINESTERASE ACTIVITY AND PROTEIN CONTENT IN REGIONS OF THE RAT BRAIN

Abstract— Pentobarbitone sodium anaesthesia was found to produce an increase in protein content in some regions of the rat brain, i.e. posterior cortex, caudate nucleus, and a decrease in protein content in the ventral cortex.
Acetylcholinesterase expressed in terms of wet weight was found to increase in the cerebellum, medulla, and to decrease in the medial cortex, hippocampus, thalamus and caudate nucleus. The changes in activity were not explicable in terms of a direct effect of the anaesthetic on the enzyme. A decrease in protein content of rat brain was observed in the frontal cortex, ventral cortex, hippocampus and caudate nucleus after electrical shocks. Following shock avoidance conditioning procedure (shuttle-box), decreases in protein content were observed in the medial cortex, posterior cortex, cerebellum and ventral cortex; in the thalamus an increase in protein content was observed.
Changes in AChE activity were observed following footshock in the frontal cortex and medulla where there was an increase in activity and in the caudate nucleus, hypothalamus, thalamus, and olfactory tubercle where there was a decrease in activity.
Following shock avoidance conditioning the activity of the AChE increased in posterior cortex, hippocampus, thalamus and hypothalamus and the activity of the enzyme decreased in the ventral cortex.     

Anatomic connections between homotopic transplant of fetal cortical tissue and optic thalamus in adult rats

The present research was planned to study the possibility to reconstruct a damaged neural circuitry by replacing the injured neurons with homotopic fetal cells. In adult rats the motor cortex was injured with intracortical injection of kainic acid solution. After a delay of 10-14 days, a block of cerebral cortex of fetal rats (E17) was transplanted in the cavity produced by the kainic acid in the motor cortex. After 2-3 months, WGA-HRP solution was injected in the thalamus of the host and both anterogradely labeled fiber terminals and retrogradely labeled somata cells were researched in the transplanted cortex. The results showed that: 1) the host thalamus projects to the transplanted cortex with less density compared to the host cortex surrounding the transplant; 2) the thalamic projection to the transplant is not topographically organized whereas the projection to the host cortex is; 3) the transplant was virtually void of a significant projection to the thalamus of the host. In conclusion, the results offer direct evidence that the reconstruction of an injured thalamocortical circuitry of adult rat is not possible by transplanting homotopic fetal neurons.     

Processing in layer 4 of the neocortical circuit: new insights from visual and somatosensory cortex

Recent experimental and theoretical results in cat primary visual cortex and in the whisker-barrel fields of rodent primary somatosensory cortex suggest common organizing principles for layer 4, the primary recipient of sensory input from the thalamus. Response tuning of layer 4 cells is largely determined by a local interplay of feed-forward excitation (directly from the thalamus) and inhibition (from layer 4 inhibitory interneurons driven by the thalamus). Feed-forward inhibition dominates excitation, inherits its tuning from the thalamic input, and sharpens the tuning of excitatory cells. Recurrent excitation enhances responses to effective stimuli.     

State-dependent sensory gating in olfactory cortex

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.     

Auditory processing in primate cerebral cortex.

Auditory information is relayed from the ventral nucleus of the medial geniculate complex to a core of three primary or primary-like areas of auditory cortex that are cochleotopically organized and highly responsive to pure tones. Auditory information is then distributed from the core areas to a surrounding belt of about seven areas that are less precisely cochleotopic and generally more responsive to complex stimuli than tones. Recent studies indicate that the belt areas relay to the rostral and caudal divisions of a parabelt region at a third level of processing in the cortex lateral to the belt. The parabelt and belt regions have additional inputs from dorsal and magnocellular divisions of the medial geniculate complex and other parts of the thalamus. The belt and parabelt regions appear to be concerned with integrative and associative functions involved in pattern perception and object recognition. The parabelt fields connect with regions of temporal, parietal, and frontal cortex that mediate additional auditory functions, including space perception and auditory memory.     

Directional indicator on neural oscillations as a measure of synaptic plasticity in chronic unpredictable stress rats

To examine whether the directionality index of neural information flow (NIF) over specific oscillatory bands is useful in measuring synaptic plasticity, we employed the IM approach to determine the direction of NIF between the cortex and thalamus in normal and stressed animals. The experiment was performed by inducing long-term potentiation (LTP) of the thalamocortical pathway after recording local field potential (LFP). Additionally, comparison of IM measurement between broad- and narrowbands was performed, while a numerical study was also carried out for assessing the number of data points. The results show that the instantaneous phases extracted from narrowband vary monotonically, while these phases are jagged in broadband. Our data show that there is a predominant driving effect (coupling directional index d >0) from the thalamus to the frontal cortex in normal animals; however, the value of d is significantly reduced in the chronic stressed group in both the delta and theta bands. Furthermore, the field LTP data show that chronic stress decreases medial prefrontal cortex synaptic plasticity, which is certainly in line with the LFP findings. Together, these data suggest that using an IM algorithm, the directionality index of NIF in specific oscillatory frequency bands will probably be used as a measure of synaptic plasticity.     

Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons

Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2–20?Hz). Stimulus trains also resulted in significant synaptic depression above 10?Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.     

Homotopic transplant of fetal cortex to lesioned motor cortex of adult rats. A comportamental and anatomical study.

Previous investigations have shown that the transplant of fetal nervous tissue in adult, formerly injured, brain induces an improvement of the neurological deficits. The process underlying this finding is not yet known. It has been proposed that this process is favourably supported by the reconstruction of the damaged circuitry, replacing the injured neurons with the transplanted fetal cells. In the present study we have investigated the relation between the improvement of the neurological deficits and the anatomical integration of the transplanted neurons within the host brain. The plan of the investigation included two steps: the first step consisted of inducing neurological deficits by kainic acid lesion of the motor cortex and then studying the changes in the motor learning following a homotopic transplant of fetal cortex in the side of the lesion. The second step consisted of studying the anatomical integration of the transplanted cortex with the thalamus of the host. The results showed that the rats with injury of the motor cortex followed by solid transplant of fetal cortex (E 17) had a significantly greater recovery of the motor learning with respect to non-transplanted rats with a lesioned motor cortex. In the same rats, the connections between the transplanted cerebral cortex and the thalamus of the host has been investigated. WGA-HRP solution was injected in the thalamus and both labeled fiber terminals and labeled cells were searched for in the transplants. The results showed that: 1) the host thalamus projects to the transplanted cortex with a lower density than to the host cortex surrounding the transplant; 2) the thalamic projection to the host cortex is topographically organized, whereas the projection to the transplant is arranged in patches without any topographical organization; 3) the transplant does not send a significant projection to the thalamus of the host. In conclusion, the experimental findings demonstrate that the reconstruction of an injured thalamo-cortical circuitry of adult rats transplanting fetal neurons is not possible. The improvement of the functional deficits by the transplant of fetal tissue may be referred to aspecific factors enhancing the functional activity of the host cortex undamaged by the initial injury. The identification of the nature of the hypothesized factors requires further investigation.     

Cre recombinase-mediated gene deletion in layer 4 of murine sensory cortical areas

Thalamocortical input to layer 4 carries the major ascending sensory information to the mammalian sensory cortex and is crucial for the function and plasticity of sensory cortical areas. Here we report identification of a Six3-cre transgene that is selectively expressed in layer 4 of sensory cortical areas but not in the thalamus. In the mature somatosensory cortex Cre recombinase expressed from the transgene is able to mediate gene deletion in the overwhelming majority of layer 4 neurons, including GABAergic interneurons. The gene deletion in layer 4 mainly occurs during the first postnatal week. This cre transgene therefore provides a useful tool for examining the role of proteins expressed in layer 4 neurons.     

Cortically-Controlled Population Stochastic Facilitation as a Plausible Substrate for Guiding Sensory Transfer across the Thalamic Gateway

The thalamus is the primary gateway that relays sensory information to the cerebral cortex. While a single recipient cortical cell receives the convergence of many principal relay cells of the thalamus, each thalamic cell in turn integrates a dense and distributed synaptic feedback from the cortex. During sensory processing, the influence of this functional loop remains largely ignored. Using dynamic-clamp techniques in thalamic slices in vitro, we combined theoretical and experimental approaches to implement a realistic hybrid retino-thalamo-cortical pathway mixing biological cells and simulated circuits. The synaptic bombardment of cortical origin was mimicked through the injection of a stochastic mixture of excitatory and inhibitory conductances, resulting in a gradable correlation level of afferent activity shared by thalamic cells. The study of the impact of the simulated cortical input on the global retinocortical signal transfer efficiency revealed a novel control mechanism resulting from the collective resonance of all thalamic relay neurons. We show here that the transfer efficiency of sensory input transmission depends on three key features: i) the number of thalamocortical cells involved in the many-to-one convergence from thalamus to cortex, ii) the statistics of the corticothalamic synaptic bombardment and iii) the level of correlation imposed between converging thalamic relay cells. In particular, our results demonstrate counterintuitively that the retinocortical signal transfer efficiency increases when the level of correlation across thalamic cells decreases. This suggests that the transfer efficiency of relay cells could be selectively amplified when they become simultaneously desynchronized by the cortical feedback. When applied to the intact brain, this network regulation mechanism could direct an attentional focus to specific thalamic subassemblies and select the appropriate input lines to the cortex according to the descending influence of cortically-defined “priors”.