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Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus (RTN) is important in regulating oscillations in the thalamocortical network, promoting those in the spindle range of frequencies over those at lower frequencies. Excitatory inputs to the RTN from the cerebral cortex are numerically large and particularly powerful in inducing spindles. However, the extent to which corticothalamic influences can engage the inhibitory network of the RTN has not been fully explored. Focal electrical stimulation of layer VI in the barrel cortex of the mouse thalamocortical slice in vitro resulted in prominent di- or polysynaptic inhibitory postsynaptic currents (IPSCs) in RTN cells under the experimental conditions used. The majority of cortically induced responses consisted of mixed PSCs in which the inhibitory component predominated or of large IPSCs alone, implying inhibition of neighboring cells by other, cortically excited RTN cells. Within the mixed PSCs, fixed and variable latency components could commonly be identified. IPSCs could be blocked by application of ionotropic glutamate receptor antagonists or of GABA(A) receptor antagonists, also indicating their dependence on corticothalamic excitation triggering disynaptic or polysynaptic inhibition. Spontaneous GABA(A) receptor-dependent IPSCs were routinely observed in the RTN and, taken together with the results of cortical stimulation, indicate the existence of a substantial network of intrareticular inhibitory connections that can be effectively recruited by the corticothalamic system. These results suggest activation of cortical excitatory inputs triggers the propagation of inhibitory currents within the RTN and support the view that activation of the RTN from the somatosensory cortex, although focused by the topography of the corticothalamic projection, is capable of disynaptically engaging the whole inhibitory network of the RTN, by local and probably by reentrant GABA(A) receptor-based synapses, thus spreading the corticothalamic influence throughout the RTN.

The development of receptor function at corticothalamic synapses during the first 20 days of postnatal development is described. Whole cell excitatory postsynaptic currents (EPSCs) were evoked in relay neurons of the ventral posterior nucleus (VP) by stimulation of corticothalamic fibers in in vitro slices of mouse brain from postnatal day 1 (P1). During P1-P12, excitatory postsynaptic conductances showed strong voltage dependence at peak current and at 100 ms after the stimulus and were almost completely antagonized by -2-amino-5-phosphonopentoic acid (APV), indicating that N-methyl--aspartate (NMDA) receptor-mediated currents dominate corticothalamic EPSCs at this time. After P12, in 42% of cells, excitatory postsynaptic conductances showed no voltage-dependence at peak current but still showed voltage-dependence 100-ms poststimulus. This voltage-dependent conductance was antagonized by APV. The nonvoltage-dependent component was APV resistant, showed fast decay, and was antagonized by the nonNMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In the remaining 58% of cells after P12, excitatory postsynaptic conductances showed moderate voltage dependence at peak conductance and strong voltage dependence 100 ms after the stimulus. Analysis of EPSCs before and after APV showed a significant increase in the relative contribution of the non-NMDA conductance after the second postnatal week. From P1 to P16, there was a significant decrease in the time constant of decay of the NMDA EPSC but no change in the voltage dependence of the NMDA response. After P8, slow EPSPs, 1.5-30 s in duration and mediated by metabotropic glutamate receptors (mGluRs), could be evoked by high-frequency stimulation of corticothalamic fibers in the presence of APV and CNQX. Similar slow depolarizations could be evoked by local application of the mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) but from P0. Both conductances were blocked by the mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine. Hence functional mGluR receptors are present on VP cells from birth, but their synaptic activation at corticothalamic synapses can only be detected after P8. In voltage clamp, the extrapolated reversal potential of the t-ACPD current, with potassium gluconate-based internal solution, was +12 +/- 10 (SE) mV, and the measured reversal potential with cesium gluconate-based internal solution was 1.5 +/- 9.9 mV, suggesting that the mGluR-mediated depolarization was mediated by a nonselective cation current. Replacement of NaCl in the external solution caused the reversal potential of the current to shift to -18 +/- 2 mV, indicating that Na+ is a charge carrier in the current. The current amplitude was not reduced by application of Cs+, Ba2+, and Cd2+, indicating that the t-ACPD current was distinct from the hyperpolarization-activated cation current (IH) and distinct from certain other previously characterized mGluR-activated, nonselective cation conductances.

Inhibitory postsynaptic potentials (IPSPs) generated by activation of the thalamic reticular nucleus (RTN) were recorded in neurons of the ventral posterior nucleus (VP) in vitro in slices from mice aged postnatal day (P)1-P17. An early IPSP peaking 41 +/- 2.5 (SE) ms after electrical stimulation of the internal capsule or RTN was found in 96% of VP neurons. This early IPSP was blocked by bicuculline, showing its dependence on gamma-aminobutyric acid-A (GABA(A)) receptors. A late IPSP peaking 357 +/- 27 ms after the stimulus was observed in 22% of VP neurons in control medium but was uncovered in 38% of neurons when bicuculline was added. The late IPSP was blocked by addition of a GABA(B) antagonist, 2-hydroxysaclofen, to the medium (n = 7); it had a reversal potential of -98 +/- 1.3 mV, 14 mV negative to the early component. In contrast to the early IPSP, whose reversal potential became more negative during postnatal development, the reversal potential of the late IPSP remained constant throughout the postnatal period studied. The most significant change in the late IPSP was shortening in duration, with reduction in latency-to-peak by >400 ms, between P1 and P10. No changes of comparable magnitude were observed in the duration of the earlier GABA(A) response. These results show that both GABA(A) and GABA(B) IPSPs are present very early in the postnatal thalamus and that their characteristics evolve along independent paths during postnatal development.

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.

1. Extracellular and intracellular methods were used to record from fibers and neurons in the ventral lateral (VL) and adjacent nuclei of the cat thalamus. The receptive fields of the recorded units were analyzed and the units tested for inputs from the medial lemniscus (ML) and spinothalamic tract (STT) by electrical stimulation of the dorsal columns (DC) and ventrolateral funiculus (VLF) at the C2-3 spinal level. 2. Thirty-eight STT fibers were isolated in the thalamus. Their conduction velocities ranged from 15 to 75 m/s (mode 36 m/s). Adequate stimuli were found for 23 of these fibers. Seventeen were low-threshold (LT), 3 were wide-dynamic-range (WDR), and 3 were high-threshold (HT) units. 3. Five STT fibers were intra-axonally injected. Three were sufficiently well filled for analysis of their terminal fields. An intermediate-velocity STT fiber (conduction velocity 38 m/s) had a 4.3-microns axon and a single large terminal field in the central lateral nucleus (CL). The other two STT fibers were smaller, with diameters of 2.5 and 2.3 microns, conduction velocities of 15 and 19 m/s, and terminal fields made up of a few small boutons at the borders of the ventral posterior lateral nucleus (VPL). 4. Of 319 neurons isolated, 14 out of 129 (10.8%) in VL, 14 out of 76 (18.4%) in the VPL or ventral posterior medial (VPM) nucleus, 27 out of 64 (42.2%) in the CL nucleus, and 5 out of 50 (10%) in the reticular nucleus (R) responded at latencies less than 50 ms to VLF stimuli. A train of three pulses was more effective in driving VLF-responding neurons in all these nuclei than a single pulse. VLF-responding cells were widely dispersed in VL, concentrated in a focus in CL, and distributed around the borders of VPL. Most of those in VL and a small number in CL could be antidromically activated by stimulation of motor cortex. 5. Latencies of presynaptic responses (STT fibers) to VLF stimulation were short and varied from 0.8 to 3.9 ms (mode 1.6 ms). Despite this, very few fast-responding neurons were found. These were six VPL neurons (2.5 to 4 ms), one VL neuron (3 ms), and four CL neurons (3-4 ms). The initial spike latencies of the majority of thalamic neurons responding to VLF stimulation appeared in two peaks, one between 6 and 8 ms and the other at 10-15 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Intracortical microstimulation (ICMS) and horseradish peroxidase (HRP) histochemistry were combined to examine the relationship between intrinsic connections and intracortical microstimulation sites eliciting evoked movements in the forelimb representation of adult macaque monkey motor cortex. 2. The distribution of sites from which stimulation-evoked movements about individual forelimb joints were elicited under anesthesia varied considerably among animals. Identical movements could often be elicited from multiple, noncontiguous sites. 3. After single, small extracellular HRP injections at sites from which thumb movement was evoked, small groups of retrogradely labeled cells and dense patches of axon terminations were found scattered across a wide area of the forelimb representation. Terminal patches were discontinuous and arose from horizontal, intracortical axons. 4. Correlating the HRP labeling with the physiologically defined movement maps revealed a profuse set of intrinsic, bidirectional connections that connect digit representations and representations of movements about the wrist, elbow, and shoulder. 5. HRP injections placed in the forelimb representation close to the physiologically defined face representation resulted in virtually no retrogradely labeled cells or terminal fiber labeling that crossed into the face representation. A patch of anterolaterally placed label that was present may be the dissociated rostrolateral arm area of other authors. 6. Taken together, these data suggest that extensive, horizontally oriented, intrinsic axon collaterals provide inputs to many different forelimb movement representations and may be recruited during complex movements to coordinate the activity of motor cortical zones whose predominant output is to forelimb muscle groups acting synchronously.

1. Medial lemniscal axons were identified by extra- and intracellular recording in the thalamic ventral posterior lateral nucleus (VPL) of cats and injected intracellularly with horseradish peroxidase (HRP). 2. Axons were characterized in terms of their latencies of response to stimulation of the medial lemniscus in the medulla, their receptive fields, and the temporal patterns of their discharge in response to stimulation of the receptive field with natural, hand-held stimuli. One-hundred sixty-six axons were placed in five operational groups: hair transient (Ht) (n = 41); hair sustained (Hs) (n = 45); pressure transient (Pt) (n = 14); pressure sustained (Ps) (n = 27), and deep or joint (Jt) (n = 39). 3. There was a tendency for Jt axons to have their terminations in anterodorsal parts of VPL and for those in the four cutaneous categories to have theirs in more central parts of the nucleus. 4. Nineteen injected axons with receptive fields mainly on the distal forelimb were subjected to detailed morphological analysis in terms of extent of terminal field and number of boutons. All axons ended in localized terminal fields that were more extensive anteroposteriorly than in the other dimensions. All showed an overall similarity and similar ranges of variation. There was a tendency, however, for Jt axons to have the least extensive terminations with fewest boutons. Ps axons had the most extensive terminations and largest number of boutons; Hs axons had small terminations and few boutons but Ht axons had small-to-medium arborizations with many boutons; no Pt axons were sufficiently well stained to enable comparisons of them with the others. There were no marked differences in axon diameter or conduction velocity among the five types. 5. Boutons identified light microscopically tended to be clustered in linear chains along proximal dendrites of relay neurons and electron microscopy revealed that they were terminals making synaptic contacts on relay cell dendrites and on presynaptic dendrites of interneurons. 6. These results reveal more similarities than differences among lemniscal axon terminations in VPL. Further studies of a quantitative nature on stimulus-response coupling and on the geographic distribution of lemniscal synapses on relay neurons will be required to reveal how lemniscal input is translated into relay cell output in VPL.

1. The third somatosensory area (SIII) was identified in the cat cerebral cortex by the recording of surface potentials evoked by deflection of a single contralateral mystacial vibrissa. A small amount of tritiated leucine was then injected at the center of the focus of evoked activity and, after a suitable survival period, the brain was prepared for autoradiography. 2. As defined by the presence of an autoradiographic injection, the SIII focus lay in a cytoarchitectonic field characterized in particular by the presence of very large pyramidal cells in layer V and corresponding to area 5a of Hassler and Muhs-Clement (24). 3. The terminal ramifications of corticothalamic cells, as outlined by axoplasmically transported label, formed clustered aggregations in the medial division of the posterior group of thalamic nuclei (Pom) and not in the ventrobasal complex (VB). This part of Pom is known to receive fibers from the spinal cord. 4. Injections of horseradish peroxidase primarily affecting area 5a retrogradely labeled cells in Pom but not in VB. 5. Injections of isotope in the two other foci of vibrissa-evoked activity usually recorded in each brain were invariably found to label a part of area 3b of the first somatosensory area (SI) in the case of the more anterior focus. The second focus sometimes lay in area 2 of SI and sometimes in the second somatosensory area (SII).