The impact of 'bursting' thalamic impulses at a neocortical synapse

Considerable effort has gone into understanding the mechanisms underlying high-frequency 'bursting' of thalamocortical impulses, their sensory information content and their involvement in perception. However, little is known about the influence of such impulses on their cortical targets. Here we follow bursting thalamic impulses to their terminus at the thalamocortical synapse of the awake rabbit, and examine their influence on a class of somatosensory cortical neurons. We show that thalamic bursts potently activate cortical circuits. Initial impulses of each burst have a greatly enhanced ability to elicit cortical action potentials, and later impulses in the burst further raise the probability of eliciting spikes. In some cases, multiple cortical spikes result from a single burst. Moreover, we show that the interval preceding each burst is crucial for generating the enhanced cortical response. The powerful activation of neocortex by thalamocortical bursts is fully consistent with an involvement of these impulses in perceptual/attentional processes.     

Cortical activation patterns evoked by afferent axons stimuli at different frequencies: an in vitro voltage-sensitive dye imaging study

Voltage-sensitive dye imaging (VDI) of cortical activation patterns generated by electrical stimulation of thalamocortical afferents axons at different frequencies was studied, in vitro, using mouse brain slices. The study demonstrated that thalamocortical afferent axons stimulation could follow frequencies as high as 120 Hz without marked reduction. By contrast the power spectral density amplitude ratio in cortical layer 4 demonstrated a rapidly sigmoidal reduction at frequencies above 60 Hz. Similar findings were obtained with direct cortical afferent axons stimulation that obviated possible interactions at thalamic level. As pre-synaptic afferent field potentials, simultaneously recorded with the VDI at cortical level, followed higher stimulation frequency, it is concluded that cortical activity reduction is secondary to synaptic transmission failure. This interpretation agrees with the result from deep-brain stimulation (DBS) in humans in which high-frequency stimulation produces comparable therapeutic results, as does stereotaxic brain lesioning.     

Different temporal processing of sensory inputs in the rat thalamus during quiescent and information processing states in vivo

Sensory inputs from the whiskers reach the primary somatosensory thalamus through the medial lemniscus tract. The main role of the thalamus is to relay these sensory inputs to the neocortex according to the regulations dictated by behavioural state. Intracellular recordings in urethane-anaesthetized rats show that whisker stimulation evokes EPSP-IPSP sequences in thalamic neurons. Both EPSPs and IPSPs depress with repetitive whisker stimulation at frequencies above 2 Hz. Single-unit recordings reveal that during quiescent states thalamic responses to repetitive whisker stimulation are suppressed at frequencies above 2 Hz, so that only low-frequency sensory stimulation is relayed to the neocortex. In contrast, during activated states, induced by stimulation of the brainstem reticular formation or application of acetylcholine in the thalamus, high-frequency whisker stimulation at up to 40 Hz is relayed to the neocortex. Sensory suppression is caused by the depression of lemniscal EPSPs in relatively hyperpolarized thalamocortical neurons. Sensory suppression is abolished during activated states because thalamocortical neurons depolarize and the depressed lemniscal EPSPs are able to reach firing threshold. Strong IPSPs may also contribute to sensory suppression by hyperpolarizing thalamocortical neurons, but during activated states IPSPs are strongly reduced altogether. The results indicate that the synaptic depression of lemniscal EPSPs and the level of depolarization of thalamocortical neurons work together in thalamic primary sensory pathways to suppress high-frequency sensory inputs during non-activated (quiescent) states while permitting the faithful relay of high-frequency sensory information during activated (processing) states.     

Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus in rats.

1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical evoked potentials (EPs) associated with electrical and chemical stimulation of nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used. Cortical EPs were produced by test stimuli delivered to a hindpaw or the thalamic ventral posterior lateral nucleus (VPL; electrical stimulation), or by photic stimulation of the eyes or electrical stimulation of contralateral homotopical cortex (transcallosal EPs). These test stimuli were then preceded by electrical or chemical conditioning stimulation (CS) delivered to NRM through a stereotaxically implanted electrode or injection cannula, respectively. Effects of CS on EPs produced by the test stimuli were characterized. 2. Electrical CS preceding a test stimulus delivered to the foot reduced the amplitude of EPs at thresholds as low as 10-25 microA. The magnitude of EP reduction was dependent on CS intensity, frequency, and the C-T interval. Optimal parameters were trains of 10 pulses (400 Hz) delivered at a C-T interval of 5-10 ms. Injection of glutamate and lidocaine into NRM demonstrated that these effects were due to activation of NRM neurons and not to current spread to medial lemniscus (ML). NRM CS also reduced cortical EPs produced by test stimulation in VPL but did not alter EPs from visual stimulation or from electrical stimulation of contralateral homotopical cortex. 3. These findings suggest that NRM CS attenuates EPs by inhibiting thalamic or thalamocortical afferent activity. Because NRM CS affected all components of the cortical EPs, the effect appears to involve alteration of general sensory activity and is not nociception specific.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synaptic interactions between thalamic and cortical inputs onto cortical neurons in vivo

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at approximately 10 ms and lasting from 60 to 100 ms. All neurons tested with thalamic followed by cortical stimuli showed a decrease in the apparent input resistance (R(in)), the time course of which paralleled that of decreased responses, suggesting that shunting is the factor accounting for EPSP's decrease. Only half of neurons tested with cortical followed by thalamic stimuli displayed changes in R(in). Spike shunting in the thalamus may account for those cases in which decreased synaptic responsiveness of cortical neurons was not associated with decreased R(in) because thalamocortical neurons showed decreased firing probability during cortical stimulation. These results suggest a short-lasting but strong shunting between thalamocortical and cortical inputs onto cortical neurons.     

Synaptic properties of thalamic and intracortical inputs to layer 4 of the first- and higher-order cortical areas in the auditory and somatosensory systems

The thalamus is an essential structure in the mammalian forebrain conveying information topographically from the sensory periphery to primary neocortical areas. Beyond this initial processing stage, "higher-order" thalamocortical connections have been presumed to serve only a modulatory role, or are otherwise functionally disregarded. Here we demonstrate that these "higher-order" thalamic nuclei share similar synaptic properties with the "first-order" thalamic nuclei. Using whole cell recordings from layer 4 neurons in thalamocortical slice preparations in the mouse somatosensory and auditory systems, we found that electrical stimulation in all thalamic nuclei elicited large, glutamatergic excitatory postsynaptic potentials (EPSPs) that depress in response to repetitive stimulation and that fail to activate a metabotropic glutamate response. In contrast, the intracortical inputs from layer 6 to layer 4 exhibit facilitating EPSPs. These data suggest that higher-order thalamocortical projections may serve a functional role similar to the first-order nuclei, whereas both are physiologically distinct from the intracortical layer 6 inputs. These results suggest an alternate route for information transfer between cortical areas via a corticothalamocortical pathway.     

Properties of primary sensory (lemniscal) synapses in the ventrobasal thalamus and the relay of high-frequency sensory inputs

The main role of the thalamus is to relay sensory inputs to the neocortex. In the primary somatosensory thalamus (ventrobasal thalamus), sensory inputs deliver tactile information through the medial lemniscus tract. The transmission of sensory information through this pathway is affected by behavioral state. For instance, the relay of high-frequency somatosensory inputs through the thalamus is suppressed during anesthesia or quiescent states but allowed during behaviorally activated states. This change may be due to the effects of modulators on the efficacy of lemniscal synapses. Here I show that lemniscal synapses of adult rodents studied in vitro produce large amplitude-highly secure unitary excitatory postsynaptic potentials (EPSPs), which depress in response to repetitive stimulation at frequencies >2 Hz. Acetylcholine and norepinephrine, which are important thalamic modulators, have no effect on the efficacy of lemniscal EPSPs but reduce evoked inhibitory postsynaptic potentials and corticothalamic EPSPs. Although acetylcholine and norepinephrine do not affect lemniscal synapses, the postsynaptic depolarization they produce on thalamocortical neurons serves to warrant the relay of lemniscal inputs at high-frequency rates by bringing the depressed lemniscal EPSPs close to firing threshold. In conclusion, acetylcholine and norepinephrine released during activated states selectively enhance sensory transmission through the lemniscal pathway by depolarizing thalamocortical neurons and simultaneously depressing the other afferent pathways.     

Thalamic and cortical high-frequency (600 Hz) somatosensory-evoked potential (SEP) components are modulated by slight arousal changes in awake subjects

Human somatosensory-evoked potentials (SEP) recorded at the scalp after conventional electrical median-nerve stimulation contain a low-amplitude (<500 nV), high-frequency (approximately 600 Hz) burst of repetitive wavelets, which are superimposed onto the primary cortical response N20. Previous electroencephalographic (EEG) studies have shown: (1) that these wavelets are generated near the hand area of the primary somatosensory cortex and in deep fibers of thalamocortical afferences; and (2) that only the 600-Hz burst, but not the N20 is decreased during sleep. Since the thalamus is involved in regulating both, selective attention and arousal, the present study aimed at characterizing the effects of focused attention and slight arousal changes on the 600-Hz oscillations. A dipole-source analysis of 64-channel SEP recordings after electric right-median-nerve stimulation allowed the comparison of brainstem, thalamic, and two cortical (one tangential, one radial) source activities in ten awake human subjects under two slightly different arousal states (eyes open vs. eyes closed), each tested for three conditions of focused attention (directed towards rare acoustic and right- or left-hand somatosensory target stimuli). While the N20 was not modified at all, the source strength of the high-frequency wavelet burst was significantly increased for eyes opened versus eyes closed, at the thalamic source site as well as for the tangentially oriented cortical source. In contrast, there were no significant differences between conditions with different attentional targets. This evidence for modulatory effects of increased arousal (eyes open) on both thalamic and cortically generated high-frequency SEP activity fits the hypothesis that the 600-Hz SEP burst at least partially represents an arousal-dependent signal generated at the thalamic level and transmitted to the primary somatosensory cortex.     

A gradient of plasticity in the amygdala revealed by cortical and subcortical stimulation, in vivo

Projections to the amygdala from various cortical and subcortical areas terminate in different nuclei. In the present study we examined long-term potentiation of synaptic transmission in the lateral or the basal amygdaloid nuclei by theta burst stimulation of thalamic vs. cortical sensory projections in the anesthetized rat. Although both the medial geniculate nucleus and the dorsal perirhinal cortex have direct projections to lateral nucleus, only the thalamic stimulation induced long-term potentiation of field potentials recorded in the lateral nucleus. In contrast, cortical (ventral perirhinal cortex) but not thalamic stimulation induced long-term potentiation in the basal nucleus.Since the thalamic pathway is believed to process simple/unimodal stimulus features, and the perirhinal cortex complex/polymodal sensory representations, the dissociation of long-term potentiation in lateral and basal nuclei suggests that the basal nucleus may serve as an amygdaloid sensory interface for complex stimulus information similar to the role of the lateral nucleus in relation to relatively simple representations. Thus plasticity of simple and complex representations may involve different amygdala inputs and circuits.     

Frequency-dependent processing in the vibrissa sensory system

The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at approximately 4-12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still (<1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1-40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1-40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception.     

Presynaptic inhibition of corticothalamic feedback by metabotropic glutamate receptors

The thalamus relays sensory information to cortex, but this information may be influenced by excitatory feedback from cortical layer VI. The full importance of this feedback has only recently been explored, but among its possible functions are influences on the processing of sensory features, synchronization of thalamic firing, and transitions in response mode of thalamic relay cells. Uncontrolled, corticothalamic feedback has also been implicated in pathological thalamic rhythms associated with certain neurological disorders. We have found a form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by a Group II metabotropic glutamate receptor (mGluR) and activated by high-frequency corticothalamic activity. We tested putative retinogeniculate and corticogeniculate synapses for Group II mGluR modulation within the dorsal lateral geniculate nucleus of the ferret thalamus. Stimulation of optic-tract fibers elicited paired-pulse depression of excitatory postsynaptic currents (EPSCs), whereas stimulation of the optic radiations elicited paired-pulse facilitation. Paired-pulse responses were subsequently used to characterize the pathway of origin of stimulated synapses. Group II mGluR agonists (LY379268 and DCG-IV) applied to thalamic neurons under voltage-clamp conditions reduced the amplitude of corticogeniculate EPSCs. Stimulation with high-frequency trains produced a facilitating response that was reduced by Group II mGluR agonists, but was enhanced by the selective antagonist LY341495, revealing a presynaptic, mGluR-mediated reduction of high-frequency corticogeniculate feedback. Agonist treatment did not affect EPSCs from stimulation of the optic tract. NAAG (reported to be selective for mGluR3) was ineffective at the corticogeniculate synapse, implicating mGluR2 in the observed effects. Our data are the first to show a synaptically elicited form of presynaptic inhibition of corticothalamic synaptic transmission that is mediated by presynaptic action of mGluR2. This presynaptic inhibition may partially mute sensory feedback and prevent reentrant excitation from initiating abnormal thalamic rhythms.     

Corticosterone differentially regulates bax,bcl-2 and bcl-x mRNA levels in the rat hippocampus

The neuronal mechanisms underlying the electroencephalographic (EEG) burst-suppression pattern are not yet understood, however, they are generally attributed to interactions within thalamocortical networks. In contrast, we report that the sensory cortex and the thalamus are disconnected, with thalamic sensory processing being unaffected by cortical EEG bursts. We studied the activity of single neurons of the somatosensory thalamocortical system in rats during burst-suppression EEG induced by the volatile anesthetic, isoflurane. In neurons of the thalamic ventrobasal complex, the discharge rate in response to tactile stimulation of their receptive fields did not differ significantly during EEG bursts and isoelectric periods. In contrast, in neurons of the primary somatosensory cortex, the response magnitude was significantly greater during EEG bursts as compared with isoelectric periods (mean increase to 293%). The results suggest that the profound suppression of cortical sensory information processing by isoflurane is suspended during EEG burst-induced elevated cortical excitation.     

The visceral sector of the thalamic reticular nucleus in the rat.

Visceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, effecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector of the thalamic reticular nucleus. No connections from the thalamic reticular nucleus have been described to the visceral sensory thalamus. We used axonal tracing techniques to study the possible existence of reciprocal connections between the visceral sensory relay in the lateral ventroposterior parvicellular thalamic nucleus, and the reticular nucleus of the thalamus. We also studied the projections from the visceral sensory cortex, located in the granular insular cortex in the rat, to the reticular nucleus of the thalamus. We found a convergent input from both thalamic and cortical sensory visceral regions to the same sector of the reticular nucleus of the thalamus. This visceral sector in turn sent GABAergic feedback connections to the lateral ventroposterior parvicellular thalamic nucleus. In addition, the visceral thalamus received histaminergic projections from the tuberomammillary nucleus, and noradrenergic projections from the locus coeruleus; both nuclei belong to the ascending activating system.Our findings indicate that the visceral sensory thalamocortical pathway is connected to the same subcortical structures that provide attention mechanisms for other thalamocortical systems.     

Nicotinic control of axon excitability regulates thalamocortical transmission

The thalamocortical pathway, a bundle of myelinated axons that arises from thalamic relay neurons, carries sensory information to the neocortex. Because axon excitation is an obligatory step in the relay of information from the thalamus to the cortex, it represents a potential point of control. We now show that, in adult mice, the activation of nicotinic acetylcholine receptors (nAChRs) in the initial portion of the auditory thalamocortical pathway modulates thalamocortical transmission of information by regulating axon excitability. Exogenous nicotine enhanced the probability and synchrony of evoked action potential discharges along thalamocortical axons in vitro, but had little effect on synaptic release mechanisms. In vivo, the blockade of nAChRs in the thalamocortical pathway reduced sound-evoked cortical responses, especially those evoked by sounds near the acoustic threshold. These data indicate that endogenous acetylcholine activates nAChRs in the thalamocortical pathway to lower the threshold for thalamocortical transmission and to increase the magnitude of sensory-evoked cortical responses. Our results show that a neurotransmitter can modulate sensory processing by regulating conduction along myelinated thalamocortical axons.     

Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.     

Adaptation in thalamic barreloid and cortical barrel neurons to periodic whisker deflections varying in frequency and velocity

Layer IV circuitry in the rodent whisker-to-barrel pathway transforms the thalamic input signal spatially and temporally. Excitatory and inhibitory barrel neurons display response properties that differ from each other and from their common thalamic inputs. Here we further examine thalamocortical response transformations by characterizing the responses of individual thalamic barreloid neurons and presumed excitatory and inhibitory cortical barrel neurons to periodic whisker deflections varying in frequency from 1 to 40 Hz. Both pulsatile and sinusoidal periodic stimulation of fixed deflection amplitude were used to assess stimulus-evoked adaptation of thalamocortical units (TCUs), fast-spike barrel units (FSUs: presumed inhibitory neurons), and regular-spike barrel units (RSUs: presumed excitatory neurons). Monotonic, frequency-dependent reductions in firing were observed in thalamic and cortical neurons to the second and subsequent stimuli in trains of high (pulsatile)- and low (sinusoidal)-velocity deflections. RSUs and FSUs adapted substantially more than their thalamic input neurons, and at all frequencies, FSUs fired at higher rates than the other two cell types. For example at 40 Hz, response magnitudes of TCUs decreased by 34%, FSUs by 72%, and RSUs by 78%. Across frequencies, RSUs and FSUs displayed more cycle-by-cycle entrainment and phase-locked responses for (high velocity) pulsatile than (lower velocity) sinusoidal deflections; for TCUs, phase-locking was equivalent for both stimuli, but entrainment was higher for sinusoidal deflections. Strong feed-forward inhibition, in conjunction with synaptic depression, renders the firing of barrel neurons sparse but temporally faithful to the occurrence of repetitive whisker deflections, especially when they are of high velocity.     

Defining cortical frequency tuning with recurrent excitatory circuitry

Neurons in the recipient layers of sensory cortices receive excitatory input from two major sources: the feedforward thalamocortical and recurrent intracortical inputs. To address their respective functional roles, we developed a new method for silencing cortex by competitively activating GABA(A) while blocking GABA(B) receptors. In the rat primary auditory cortex, in vivo whole-cell recording from the same neuron before and after local cortical silencing revealed that thalamic input occupied the same area of frequency-intensity tonal receptive field as the total excitatory input, but showed a flattened tuning curve. In contrast, excitatory intracortical input was sharply tuned with a tuning curve that closely matched that of suprathreshold responses. This can be attributed to a selective amplification of cortical cells' responses at preferred frequencies by intracortical inputs from similarly tuned neurons. Thus, weakly tuned thalamocortical inputs determine the subthreshold responding range, whereas intracortical inputs largely define the tuning. Such circuits may ensure a faithful conveyance of sensory information.     

Induction of high frequency activity in the somatosensory thalamus of rats in vivo results in long-term potentiation of responses in SI cortex

Summary Extracellular single-unit techniques were employed to record unitary activity simultaneously from the thalamic ventral posterior medial (VPM) nucleus and the ipsilateral primary somatosensory cortex of adult rats. Cross-correlation analysis triggered by the spontaneous firing of thalamocortical relay neurons in VPM and the discharge of layer IV neurons in the corresponding ipsilateral cortical barrel indicated that the paired-units included in this study were strongly correlated in their activity. The baseline responses of highly correlated cortical/thalamic pairs to a 10 ms deflection of a vibrissa on the contralateral side were measured using poststimulus time histograms. After establishing the baseline response, high frequency activity in VPM was induced in one of two ways: i) direct electrical stimulation of thalamic neurons or ii) whisker stimulation in the presence of bicuculline methiodide (BIC) released near the thalamic neurons. Both methods resulted in a conditioning stimulus (CS) paradigm consisting of bursts of high-frequency activity (50–100 Hz) with an inter-burst interval of 150 ms (7 Hz). Almost immediately following the presentation of the CS, the response of layer IV cortical neurons to vibrissa stimulation increased by 37–62% over baseline values, which was maintained after the effects of BIC had worn off in VPM. This enhancement in the response of the cortical neurons was not accompanied by a concomitant increase in the thalamic responses. Thus, these results strongly suggest that the potentiation first occurred at the thalamocortical synapse.     

EEG slow (approximately 1 Hz) waves are associated with nonstationarity of thalamo-cortical sensory processing in the sleeping human

Intracellular studies reveal that, during slow wave sleep (SWS), the entire cortical network can swing rhythmically between extremely different microstates, ranging from wakefulness-like network activation to functional disconnection in the space of a few hundred milliseconds. This alternation of states also involves the thalamic neurons and is reflected in the EEG by a slow (<1 Hz) oscillation. These rhythmic changes, occurring in the thalamo-cortical circuits during SWS, may have relevant, phasic effects on the transmission and processing of sensory information. However, brain reactivity to sensory stimuli, during SWS, has traditionally been studied by means of sequential averaging, a procedure that necessarily masks any short-term fluctuation of responsiveness. The aim of this study was to provide a dynamic evaluation of brain reactivity to sensory stimuli in naturally sleeping humans. To this aim, single-trial somatosensory evoked potentials (SEPs) were grouped and averaged as a function of the phase of the ongoing sleep slow (<1 Hz) oscillation. This procedure revealed a dynamic profile of responsiveness, which was conditioned by the phase of the spontaneous sleep EEG. Overall, the amplitude of the evoked potential changed sistematically, increasing and approaching wakefulness levels along the negative slope of the EEG oscillation and decaying below SWS average levels along the positive drift. These marked and fast changes of stimulus-correlated electrical activity involved both short (N20) and long latency (P60 and P100) components of SEPs. In addition, the observed short-term response variability appeared to be centrally generated and specifically related to the evolution of the spontaneous oscillatory pattern. The present findings demonstrate that thalamo-cortical processing of sensory information is not stationary in the very short period (approximately 500 ms) during natural SWS.     

Prenatal development of neural excitation in rat thalamocortical projections studied by optical recording

To elucidate the formation of early thalamocortical synapses we recorded optical images with voltage-sensitive dyes from the cerebral cortex of prenatal rats by selective thalamic stimulation of thalamocortical slice preparations. At embryonic day (E) 17, thalamic stimulation elicited excitation that rapidly propagated through the internal capsule to the cortex. These responses lasted less than 15 ms, and were not affected by the application of glutamate receptor antagonists, suggesting that they might reflect presynaptic fiber responses. At E18, long-lasting (more than 300 ms) responses appeared in the internal capsule and in subplate. By E19, long-lasting responses increased in the cortical subplate. By E21, shortly before birth, the deep cortical layers were also activated in addition to the subplate. These long-lasting responses seen in the internal capsule and subplate were blocked by the antagonist perfusion, but the first spike-like responses still remained. The laminar location of the responses was confirmed in the same slices by Nissl staining and subplate cells were labeled by birthdating with bromodeoxyuridine at E13. Our results demonstrate that there is a few days delay between the arrival of thalamocortical axons at the subplate at E16 and the appearance of functional thalamocortical synaptic transmission at E19. Since thalamocortical connections are already functional within the subplate and in the deep cortical plate at embryonic ages, prenatal thalamocortical synaptic connections could influence cortical circuit formation before birth.