Thalamocortical Interactions Research Articles

Brain activity relating to the contingent negative variation: an fMRI investigation

The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention, yet its functional neuroanatomical basis is poorly understood. We used functional magnetic resonance imaging (fMRI) with simultaneous EEG and recording of galvanic skin response (GSR) to investigate CNV-related central neural activity and its relationship to peripheral autonomic arousal. In a group analysis, blood oxygenation level dependent (BOLD) activity during the period of CNV generation was enhanced in thalamus, somatomotor cortex, bilateral midcingulate, supplementary motor, and insular cortices. Enhancement of CNV-related activity in anterior and midcingulate, SMA, and insular cortices was associated with decreases in peripheral sympathetic arousal. In a subset of subjects in whom we acquired simultaneous EEG and fMRI data, we observed activity in bilateral thalamus, anterior cingulate, and supplementary motor cortex that was modulated by trial-by-trial amplitude of CNV. These findings provide a likely functional neuroanatomical substrate for the CNV and demonstrate modulation of components of this neural circuitry by peripheral autonomic arousal. Moreover, these data suggest a mechanistic model whereby thalamocortical interactions regulate CNV amplitude.

Tactile Discrimination Task Not Disturbed by Thalamic Stimulation

The major pathway of human somatosensation passes through the ventrocaudal nucleus (Vc) of the thalamus. We tested the effect of direct electrical stimulation of the Vc on tactile discrimination in 5 Parkinson patients undergoing stereotactic thalamotomy. Raised gratings with lines 3, 4, or 6 mm apart were used. Patients had to actively touch test patterns placed in the hand contralateral to the thalamus under operation and compare it with a reference 3-mm grating held continuously in their other hand. Their performance was best for 6-mm, followed by 3-mm and then by 4-mm patterns regardless of electrical stimulation. Under Vc stimulation, patients recognized the 4-mm gratings slightly better. This can be explained either by the nature of thalamocortical interaction, which makes it resistant to external noise, or by the involvement of other pathways that circumvent the effect of thalamic stimulation.

Tremor in Parkinson's disease

Rest tremor is a common feature of Parkinson's disease, but its underlying pathophysiology remains unknown. This review hypothesizes that tremor is related to selective loss of components of the substantia nigra. The relative scarcity of tremor in related Parkinsonian conditions may indicate a dissociation associated with different pathological involvement of the substantia nigra and its connections. Connections of the subthalamic nucleus with the pallidum, modified by cortical and nigral inputs, allow for the transfer of tremorogenic activity to the thalamus. Thalamo-cortical interactions, tempered by cerebellar input, generate the final common pathway for tremor production.

Toward an integrated continuum model of cerebral dynamics: the cerebral rhythms, synchronous oscillation and cortical stability

Continuum models of cerebral cortex with parameters derived from physiological data, provide explanations of the cerebral rhythms, synchronous oscillation, and autonomous cortical activity in the gamma frequency range, and suggest possible mechanisms for dynamic self-organization in the brain. Dispersion relations and derivations of power spectral response for the models, show that a low frequency resonant mode and associated travelling wave solutions of the models’ equations of state can account for the predominant 1/ f spectral content of the electroencephalogram (EEG). Large scale activity in the alpha, beta, and gamma bands, is accounted for by thalamocortical interaction, under regulation by diffuse cortical excitation. System impulse responses can be used to model Event-Related Potentials. Further classes of local resonance may be generated by rapid negative feedbacks at active synapses. Activity in the gamma band around 40 Hz, associated with large amplitude oscillations of pulse density, appears at higher levels of cortical activation, and is unstable unless compensated by synaptic feedbacks. Control of cortical stability by synaptic feedbacks offers a partial account of the regulation of autonomous activity within the cortex. Synchronous oscillation occurs between concurrently excited cortical sites, and can be explained by analysis of wave motion radiating from each of the co-active sites. These models are suitable for the introduction of learning rules—most notably the coherent infomax rule.

Primary neonatal thalamic haemorrhage and epilepsy with continuous spike-wave during sleep: a longitudinal follow-up of a possible significant relation

Epilepsy with continuous spike-waves during sleep was diagnosed in a child who suffered primary neonatal thalamic haemorrhage, and who was followed from birth to 17 years of age. Early cognitive development was normal. Acquired behavioural problems and cognitive stagnation could be directly related to the epilepsy and not to the initial lesion and posthaemorrhagic hydrocephalus.This case and long-term follow-up data on a few children who suffered primary neonatal thalamic haemorrhage suggest that epilepsy with continuous spike-waves during sleep can be a sequel. Disturbances of thalamocortical interactions could play a role in the still poorly understood syndrome of epilepsy with continuous spike-waves during sleep.

Development and Evolution of Thalamocortical Interactions

Thalamocortical projections in mammals must travel through a considerable portion of the newly formed subdivisions of the embryonic forebrain. They descend through the ventral thalamus, advance in the internal capsule amongst cells which already possess dorsal thalamic projections, traverse the striatocortical junction, and then reach the cerebral cortex by associating with subplate cells and their early corticofugal fibers. The interactions of the thalamocortical projections with early generated, largely transient cells of these regions are believed to play a crucial role in their deployment. These ideas are supported by recent work on reeler and other strains of mutant mice. While we are beginning to understand the basic pattern of the cellular and molecular interactions employed in mammalian thalamocortical development, comparative developmental studies hold the promise to reveal the underlying logic of these steps and the evolutionary origin of the mammalian cerebral cortex.

Development and Evolution of Thalamocortical Interactions

Development and Evolution of Thalamocortical Interactions

Corticothalamic Inputs Control the Pattern of Activity Generated in Thalamocortical Networks

Absence seizures (3-4 Hz) and sleep spindles (6-14 Hz) occur mostly during slow-wave sleep and have been hypothesized to involve the same corticothalamic network. However, the mechanism by which this network transforms from one form of activity to the other is not well understood. Here we examine this question using ferret lateral geniculate nucleus slices and stimulation of the corticothalamic tract. A feedback circuit, meant to mimic the cortical influence in vivo, was arranged such that thalamic burst firing resulted in stimulation of the corticothalamic tract. Stimuli were either single shocks to mimic normal action potential firing by cortical neurons or high-frequency bursts (six shocks at 200 Hz) to simulate increased cortical firing, such as during seizures. With one corticothalamic stimulus per thalamic burst, 6-10 Hz oscillations resembling spindle waves were generated. However, if the stimulation was a burst, the network immediately transformed into a 3-4 Hz paroxysmal oscillation. This transition was associated with a strong increase in the burst firing of GABAergic perigeniculate neurons. In addition, thalamocortical neurons showed a transition from fast (100-150 msec) IPSPs to slow ( approximately 300 msec) IPSPs. The GABA(B) receptor antagonist CGP 35348 blocked the slow IPSPs and converted the 3-4 Hz paroxysmal oscillations back to 6-10 Hz spindle waves. Conversely, the GABA(A) receptor antagonist picrotoxin blocked spindle frequency oscillations resulting in 3-4 Hz oscillations with either single or burst stimuli. We suggest that differential activation of thalamic GABA(A) and GABA(B) receptors in response to varying corticothalamic input patterns may be critical in setting the oscillation frequency of thalamocortical network interactions.

Development of thalamocortical projections in normal and mutant mice.

In vitro and in vivo studies have begun to reveal multiple mechanisms involved in the development of thalamocortical projections. Different cellular and molecular interactions dominate during the various stages of axon elongation, target selection, and establishment of layer- and area-specific connections. Recent work points to the crucial role of the early-developing thalamocortical projections and their interactions with the developing cortical circuitry in establishing the functional and structural organization of the cortex. In this chapter we give an overview of mutant mice, including knockout (KO) mice which have homozygous null gene mutations, which are providing interesting paradigms for distinct phases of thalamocortical development. We present selected mutants in two major groups. The first group involves mutations that directly influence some key mechanism of axon elongation and delivery (reeler mutant, L1 KO, TBR-1 KO, Pax-6 KO) or thalamocortical interactions (Adcyl Barrelless, MAO-A KO, NMDA receptor mutant, PLC-β1 KO, GAP-43 KO). The second group (albino, anophthalmic mice, mice with extra vibrissae) includes mutations that do not affect thalamocortical outgrowth or the interactions between thalamic projections and cortical circuitry itself, but instead alter the sensory flow of information from the periphery and influence thalamocortical development. The number of available mutants is increasing rapidly and, combined with recent technology allowing gene expression to be experimentally manipulated in precise spatiotemporal patterns, will provide further understanding of the development and plasticity of thalamocortical connections.

Dynamic properties of corticothalamic excitatory postsynaptic potentials and thalamic reticular inhibitory postsynaptic potentials in thalamocortical neurons of the guinea-pig dorsal lateral geniculate nucleus

The properties of postsynaptic potentials evoked by stimulation of cortical, retinal and GABAergic thalamic afferents were examined in vitro in thalamocortical neurons of the guinea-pig dorsal lateral geniculate nucleus. Brief trains of stimulation (2–10 stimuli) delivered to corticothalamic fibers led to a frequency-dependent increase in excitatory postsynaptic potential amplitude associated with an increase in activation of both N-methyl- d-aspartate and non- N-methyl- d-aspartate glutamate receptors. In addition, repetitive stimulation of corticothalamic fibers also gave rise to a slow excitatory postsynaptic potential that was blocked by local application of the glutamate metabotropic receptor antagonist α-methyl-4-carboxyphenylglycine. In contrast, repetitive stimulation of optic tract fibers resulted in monosynaptic excitatory postsynaptic potentials that did not potentiate and were not followed by the generation of a slow excitatory postsynaptic potential. Repetitive activation of the optic radiation also evoked both GABA A and GABA B receptor-mediated inhibitory postsynaptic potentials. These inhibitory postsynaptic potentials exhibited frequency-dependent depression during repetitive activation. The presence of frequency-dependent facilitation of corticothalamic excitatory postsynaptic potentials and frequency-dependent decrement of inhibitory postsynaptic potentials, as well as the ability of corticothalamic fibers to activate glutamate metabotropic receptors, suggests that sustained activation of corticothalamic afferents in vivo may result in postsynaptic responses in thalamocortical cells that are initially dominated by GABAergic inhibitory postsynaptic potentials followed by prominent monosynaptic excitatory postsynaptic potentials as well as a slow depolarization of the membrane potential. Therefore, the corticothalamic system may inhibit or enhance the excitability and responsiveness of thalamocortical neurons, based both on the spatial and temporal features of thalamocortical interactions.

Thalamo-cortical interactions modeled by weakly connected oscillators: could the brain use FM radio principles?

We consider all models of the thalamo-cortical system that satisfy the following two assumptions: (1) each cortical column is an autonomous oscillator; (2) connections between cortical columns and the thalamus are weak. Our goal is to deduce from these assumptions general principles of thalamo-cortical interactions that are independent of the equations describing the system. We find that the existence of synaptic connections between any two cortical columns does not guarantee that the columns interact: They interact only when there is a certain nearly resonant relation between their frequencies, which implies that the interactions are frequency modulated (FM). When the resonance relation holds, the cortical columns interact through phase modulations. Thus, communications between weakly connected cortical oscillators employ a principle similar to that in FM radio: The frequency of oscillation encodes the channel of communication, while the information is transmitted via phase modulations. If the thalamic input has an appropriate frequency, then it can dynamically link any two cortical columns, even those that have non-resonant frequencies and would otherwise be unlinked. Thus, by adjusting its temporal activity, the thalamus has control over information processing taking place in the cortex. Our results suggest that the mean firing rate (frequency) of periodically spiking neuron does not carry any information other than identifying a channel of communication. Information (i.e. neural code) is carried through modulations of interspike intervals.

605 Effects of context on ERPs elicited by go and no go stimuli in a 3-stimulus paradigm

The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention, yet its functional neuroanatomical basis is poorly understood. We used functional magnetic resonance imaging (fMRI) with simultaneous EEG and recording of galvanic skin response (GSR) to investigate CNV-related central neural activity and its relationship to peripheral autonomic arousal. In a group analysis, blood oxygenation level dependent (BOLD) activity during the period of CNV generation was enhanced in thalamus, somatomotor cortex, bilateral midcingulate, supplementary motor, and insular cortices. Enhancement of CNV-related activity in anterior and midcingulate, SMA, and insular cortices was associated with decreases in peripheral sympathetic arousal. In a subset of subjects in whom we acquired simultaneous EEG and fMRI data, we observed activity in bilateral thalamus, anterior cingulate, and supplementary motor cortex that was modulated by trial-by-trial amplitude of CNV. These findings provide a likely functional neuroanatomical substrate for the CNV and demonstrate modulation of components of this neural circuitry by peripheral autonomic arousal. Moreover, these data suggest a mechanistic model whereby thalamocortical interactions regulate CNV amplitude.

Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells.

Early studies have shown that spindle oscillations are generated in the thalamus and are synchronized over wide cortical territories. More recent experiments have shown that this large-scale synchrony depends on the integrity of corticothalamic feedback. Previously proposed mechanisms emphasized exclusively intrathalamic mechanisms to generate the synchrony of these oscillations. In the present paper, we propose a cellular mechanism in which the synchrony is dependent of a mutual interaction between cortex and thalamus. This cellular mechanism is tested by computational models consisting of pyramidal cells, interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data on intrinsic currents and synaptic receptors present in the circuitry. The model suggests that corticothalamic feedback must operate on the thalamus mainly through excitation of GABAergic RE neurons, therefore recruiting relay cells essentially through inhibition and rebound. We provide experimental evidence for such dominant inhibition in the lateral posterior nucleus. In these conditions, the model shows that cortical discharges optimally evoked thalamic oscillations. This feature is essential to the present cellular mechanism and is also consistently observed experimentally. The model further shows that, with this type of corticothalamic feedback, cortical discharges recruited large areas of the thalamus because of the divergent cortex-to-RE and RE-to-TC axonal projections. Consequently, the thalamocortical network generated patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes the important role of the modulation of the Ih current by calcium in TC cells. This property conferred a relative refractoriness to the entire network, a feature also observed experimentally, as we show here. Further, the same property accounted for various spatiotemporal features of oscillations, such as systematic propagation after low-intensity cortical stimulation, local oscillations, and more generally, a high variability in the patterns of spontaneous oscillations, similar to in vivo recordings. We propose that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions in which the corticothalamic feedback acts predominantly through the RE nucleus. Several predictions are suggested to test the validity of this model.

Nonlinear processing of tactile information in the thalamocortical loop.

Rats explore tangible objects in a manner such that, at any given moment in time, multiple facial whiskers simultaneously contact the surface of the object. Although both thalamic and cortical neurons responsible for processing such tactile information have large, multiwhisker receptive fields, it remains unclear what kinds of computations can be carried out by these neuronal populations when behaviorally relevant multiwhisker stimuli are used. By simultaneously recording the activity of up to 78 cortical and thalamic neurons per animal, we observed that the magnitude of sensory responses and the spatial spread of ensemble activity increased in a nonlinear fashion according to the extent and spatial orientation of the multiwhisker stimuli. Supralinear responses were seen more frequently with vertically than with horizontally oriented stimuli. These data suggest that thalamocortical interactions in the rat somatosensory system can generate complex spatial transformations of multiwhisker stimuli that go beyond the classic inhibitory interactions previously observed.

Functional Neuroimaging of Cortical Dysfunction in Alcoholic Korsakoff's Syndrome

Many neuropsychological investigations of human memory have focused on the amnesic deficits of alcoholic Korsakoff's syndrome. Structural neuroimaging suggests that the syndrome results from midline diencephalic damage, but functional neuroimaging has the potential to reveal additional neuropathology that may be responsible for cognitive dysfunction. Accordingly, high-resolution positron emission tomography (PET) was used to measure regional cerebral metabolic rates for glucose utilization in five alcoholic Korsakoff patients and nine alcoholic control subjects. Results from a continuous recognition test administered during the radiotracer uptake period indicated that all subjects performed normally with respect to immediate memory, whereas Korsakoff patients demonstrated a marked memory impairment in delayed recognition. PET results from the Korsakoff group showed a widespread decline in glucose metabolism in frontal, parietal, and cingulate regions, suggesting that these functional abnormalities in the cerebral cortex contribute to the memory impairment. Hippocampal glucose metabolism did not differ between the groups. Thus, the evidence did not support the hypothesis that parallel brain dysfunctions are responsible for the similar amnesic symptomatology after hippocampal and diencephalic damage. We hypothesize that the amnesic dysfunction of Korsakoff's syndrome depends on a disruption of thalamocortical interactions that mediate a function critical for normal memory storage.

1809 Neuronal connectivity among barrels in the rat barrel cortex

We studied auditory thalamocortical interactions in vitro, using an auditory thalamocortical brain slice preparation. Cortical activity evoked by electrical stimulation of the medial geniculate nucleus (MGN) was investigated through field potential recordings and voltage sensitive dyes. Experiments were performed in slices obtained from adult mice (9–14 weeks). Stimulus evoked activity was detected in the granular and supragranular layers after a short latency (5–6 ms). In 9–14 weeks old mice infragranular activity was detected in 10 of 24 preparations and was found to be increased in younger mice (p 31–64). In 14 of 24 slices a prominent horizontal spread was observed, which extended into cortical areas lateral to A1. In these experiments, the shortest onset latencies and largest signal amplitudes were located in the supragranular layers of A1. In areas lateral to A1, shortest onset latencies were located in the granular layer, while largest signal amplitudes were found in the supragranular layers. Evoked cortical activity was sensitive to removal of extracellular Ca2+ or application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM). Short repetitive stimulation, resembling thalamic burst activity (three pulses at 100 Hz), resulted in an increase of signal amplitude and excited area by ∼25%, without changing the overall spatiotemporal activity profile. Blockade of N-methyl-d-aspartate receptors by 2-amino-5-phosphonopentanoate (AP5, 50 μM) reduced amplitudes and excited area by ∼15–30%, irrespective of stimulation frequency. Application of bicuculline (10 μM) greatly increased cortical responses to thalamic stimulation. Under these conditions, evoked activity displayed a pronounced horizontal spread in combination with a 2–3-fold increase in amplitude. In conclusion, afferent thalamic inputs primarily activate supragranular and granular layers in the auditory cortex of adult mice. This activation is predominantly mediated by non-NMDA receptors, while GABAA receptor-mediated inhibition limits the horizontal and vertical spread of activity.

Neuronal connectivity among barrels in the rat barrel cortex

We studied auditory thalamocortical interactions in vitro, using an auditory thalamocortical brain slice preparation. Cortical activity evoked by electrical stimulation of the medial geniculate nucleus (MGN) was investigated through field potential recordings and voltage sensitive dyes. Experiments were performed in slices obtained from adult mice (9–14 weeks). Stimulus evoked activity was detected in the granular and supragranular layers after a short latency (5–6 ms). In 9–14 weeks old mice infragranular activity was detected in 10 of 24 preparations and was found to be increased in younger mice (p 31–64). In 14 of 24 slices a prominent horizontal spread was observed, which extended into cortical areas lateral to A1. In these experiments, the shortest onset latencies and largest signal amplitudes were located in the supragranular layers of A1. In areas lateral to A1, shortest onset latencies were located in the granular layer, while largest signal amplitudes were found in the supragranular layers. Evoked cortical activity was sensitive to removal of extracellular Ca2+ or application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM). Short repetitive stimulation, resembling thalamic burst activity (three pulses at 100 Hz), resulted in an increase of signal amplitude and excited area by ∼25%, without changing the overall spatiotemporal activity profile. Blockade of N-methyl-d-aspartate receptors by 2-amino-5-phosphonopentanoate (AP5, 50 μM) reduced amplitudes and excited area by ∼15–30%, irrespective of stimulation frequency. Application of bicuculline (10 μM) greatly increased cortical responses to thalamic stimulation. Under these conditions, evoked activity displayed a pronounced horizontal spread in combination with a 2–3-fold increase in amplitude. In conclusion, afferent thalamic inputs primarily activate supragranular and granular layers in the auditory cortex of adult mice. This activation is predominantly mediated by non-NMDA receptors, while GABAA receptor-mediated inhibition limits the horizontal and vertical spread of activity.

Brightness perception, illusory contours, and corticogeniculate feedback.

A neural network model is developed to explain how visual thalamocortical interactions give rise to boundary percepts such as illusory contours and surface percepts such as filled-in brightnesses. Top-down feedback interactions are needed in addition to bottom-up feed-forward interactions to simulate these data. One feedback loop is modeled between lateral geniculate nucleus (LGN) and cortical area V1, and another within cortical areas V1 and V2. The first feedback loop realizes a matching process which enhances LGN cell activities that are consistent with those of active cortical cells, and suppresses LGN activities that are not. This corticogeniculate feedback, being endstopped and oriented, also enhances LGN ON cell activations at the ends of thin dark lines, thereby leading to enhanced cortical brightness percepts when the lines group into closed illusory contours. The second feedback loop generates boundary representations, including illusory contours, that coherently bind distributed cortical features together. Brightness percepts form within the surface representations through a diffusive filling-in process that is contained by resistive gating signals from the boundary representations. The model is used to simulate illusory contours and surface brightness induced by Ehrenstein disks, Kanizsa squares, Glass patterns, and café wall patterns in single contrast, reverse contrast, and mixed contrast configurations. These examples illustrate how boundary and surface mechanisms can generate percepts that are highly context-sensitive, including how illusory contours can be amodally recognized without being seen, how model simple cells in V1 respond preferentially to luminance discontinuities using inputs from both LGN ON and OFF cells, how model bipole cells in V2 with two colinear receptive fields can help to complete curved illusory contours, how short-range simple cell groupings and long-range bipole cell groupings can sometimes generate different outcomes, and how model double-opponent, filling-in and boundary segmentation mechanisms in V4 interact to generate surface brightness percepts in which filling-in of enhanced brightness and darkness can occur before the net brightness distribution is computed by double-opponent interactions.

Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation.

Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

Two types of interneuron in the dorsal lateral geniculate nucleus of the rat: a combined NADPH diaphorase histochemical and GABA immunocytochemical study.

The rationale for this study was to provide a comprehensive light microscopical description of the morphology of diaphorase-reactive neurons and neuropil elements in the dorsal lateral geniculate nucleus (dLGN) of the rat. An additional objective was to quantitatively assess whether a subpopulation of the diaphorase-reactive neurons, previously shown to be GABA-immunoreactive, constitute a distinct type of local-circuit neuron in the rat dLGN. Diaphorase activity was localised in a population of predominantly bipolar fusiform neurons. These cells were weak to moderately stained and possessed the morphological features of intrinsic inhibitory neurons, previously called class B neurons in the rat dLGN. Quantitative estimates indicated that the diaphorase-reactive neurons constituted approximately 10% of the total neuron composition of the dLGN. The majority (about 83%) of the diaphorase-reactive cells were located in the lateral half of the nucleus. In addition, a dense plexus of diaphorase-reactive varicose fibres was found throughout the dLGN lying between the oriented fibre bundles coursing dorsoventrally through the LGN. Diaphorase-reactive punctae were found to be closely associated with the somata and proximal dendritic segments of nonreactive neurons and also with the stained proximal dendritic segments of diaphorase-reactive dLGN neurons. The source of the diaphorase-reactive fibres in the dLGN was unknown. Evidence suggests, however, that they are of extrinsic origin. The GABA-immunoreactive nature of the diaphorase neurons in the dLGN was demonstrated by colocalising GABA immunoreactivity within the somata of diaphorase-reactive cells. The majority (> 90%) of diaphorase-reactive dLGN neurons were GABA-immunopositive. Also present was a distinct population of GABA-immunopositive neurons that were not diaphorase-reactive. In this study, cells that were solely GABA-immunopositive have been called class B1 neurons, while cells that were both diaphorase-reactive and GABA-immunoreactive have been called class B2 neurons. Size-frequency distributions of somatic profile areas established that the two populations of GABA-immunoreactive neuron were significantly different. Class B1 neurons constituted 57%, with class B2 cells representing 43% of all GABA-immunostained neurons in the rat dLGN. The characteristic morphological features, neurochemical identity and frequency of the diaphorase-reactive neurons in the rat dLGN indicate that they represent a subpopulation of inhibitory interneurons with the ability to affect intrinsic dLGN operations and thalamocortical interactions using the neuromodulator nitric oxide.