A study of the organization of the locus coeruleus projections to the lateral geniculate nuclei in the albino rat

The lateral geniculate nuclei of the rat are known to receive an innervation from catecholamine-containing neurons. In the present study the origin, axonal projections and terminal distribution of this innervation was studied. The lateral geniculate nuclei contain a356 ± 20 ng norepinephrine/g and64 ± 7 ng dopamine/g tissue; the latter is within the range expected for dopamine as a precursor in a region innervated by a norepinephrine-containing terminal system. When separate norepinephrine-containing cell groups located at various brain stem levels are ablated or their axonal projections destroyed, only lesions in the locus coeruleus produce a significant decrease in the norepinephrine content of the lateral geniculate nuclei. Injections of horseradish peroxidase into the lateral geniculate nuclei result in retrograde transport of horseradish peroxidase only to the noradrenergic neurons of the locus coeruleus. The labelled neurons are pretent throughout the rostrocaudal and dorsoventral axes of both the ipsilateral (60%) and contralateral (40%) nucleus. Autoradiographic and fluorescence histo-chemical experiments indicate that axons that ascend from the locus coeruleus reach the lateral geniculate nuclei via the dorsal tegmental catecholamine-containing bundle and the medial forebrain bundle. These fibers enter the ventral lateral geniculate nucleus from the zona incerta and the dorsal lateral geniculate nucleus from the superior thalamic radiation, thalamic reticular nucleus, and lateral posterior nucleus. Contralateral fibers from the locus coeruleus cross in the posterior commissure, supraoptic and pontine decussations and join the ipsilateral projections to the lateral geniculate nuclei. The bilateral locus coeruleus innervation of the nuclei is comprised of a highly branched network of varicose axons. Neither the ipsilateral nor the contralateral projections appear to be topographically organized; instead, a single fiber may have collateral axons that branch throughout large areas of the nuclei. This innervation is moderately dense in the ventral, and very dense in the dorsal, lateral geniculate nucleus.The study indicates that both the dorsal and ventral lateral geniculate nuclei receive a diffuse catecholamine-containing innervation which arises solely from the norepinephrine-containing neurons of the locus coeruleus. The innervation of each lateral geniculate nucleus is bilateral, with noradrenergic neurons located throughout both the ipsilateral and the contralateral locus coeruleus contributing to ascending pathways that terminate as a diffuse, plexiform innervation interspersed among other afferents to the lateral geniculate nuclei. It is speculated that such a diffuse noradrenergic innervation might depress the spontaneous activity of neurons in the lateral geniculate nuclei, while preserving or enhancing their responsiveness to afferent optic stimulation.     

Auditory neurons in the rat thalamic reticular nucleus

Summary In the thalamic reticular nucleus (TR) of the rat a cluster of neurons has been located which receives auditory inputs and acts as a source of inhibition for relay neurons of the medial geniculate nucleus (MG). These TR neurons (auditory thalamic reticular neurons; A-TR neurons) showed a repetitive burst of grouped discharge upon electrical stimulation of the inferior colliculus (IC) or of the auditory cortex. Many of them responded to tonal stimuli such as clicks or pips.Adjacent to the cluster of A-TR neurons there were the cluster of TR neurons receiving visual inputs (V-TR neurons) and that receiving somatosensory inputs (S-TR neurons). The cluster of A-TR neurons was situated ventrally to the cluster of V-TR neurons, both extending caudally from the level of the rostral tip of the dorsal lateral geniculate nucleus. The S-TR neurons distributed rostrally to the clusters of A- and V-TR neurons. Some of the sensory TR neurons, usually found around the boundaries between the clusters of different sensory modalities, were activated from stimulation of different central sensory pathways.Single electric shocks directly applied to the cluster of A-TR neurons suppressed discharges of relay neurons of the MG, either spontaneous or evoked by click stimuli or by electric shocks to the IC. The postexcitatory suppression of MG relay neurons was similar in time course to the suppression following electrical stimulation of A-TR neurons.Response latencies of the A-TR neurons to IC shocks were found to be 1.0–1.5 ms longer than those of the MG relay cells with respect to the modal and shortest values. It is suggested that A-TR neurons are intercalated in the axon collateral circuit of the thalamocortical projection arising from relay neurons of the MG.Dedicated to Dr. Kitsuya Iwama, Emeritus Professor of Osaka University Medical School, on the occasion of his retirement     

Functional distinction of perigeniculate and thalamic reticular neurons in the cat

Summary Two types of neurons can be recognized in the region above the lateral geniculate nucleus. One cell type is found in the caudal part of the reticular nucleus of thalamus; these cells are accordingly called reticular neurons. The other cell type is located in the perigeniculate nucleus immediately above lamina A of the lateral geniculate nucleus and in the intermediate zone between the perigeniculate nucleus and the reticular nucleus. These cells are referred to as perigeniculate neurons. Electrical stimulation of the optic tract and the visual cortex typically evokes a short burst of spikes in the perigeniculate neurons, and the excitation has a shorter latency from the cortex (range 1.2–2.5 ms) than from the optic tract (range 1.5–3.1 ms). The perigeniculate neurons are also activated by adequate visual stimuli. In contrast, the reticular neurons are unresponsive to visual stimuli and electrical stimulation of the optic tract but they may respond with a burst of spikes to cortex stimulation with rather long latency (range 2.7–5.5 ms). It is concluded that only perigeniculate neurons qualify as interneurons in the recurrent inhibitory pathway to principal cells in the lateral geniculate nucleus.Supported by Magnus Bergvalls Stiftelse and The Swedish Medical Research Council (Project no. 4767)F.-S. Lo had an exchange fellowship from the Royal Swedish Academy of Engineering     

Feedback inhibition in the cat's lateral geniculate nucleus

Feedback inhibition is generally believed to be a ubiquitous feature of brain circuitry, but few specific instances have been documented. An example in cats is the supposed feedback circuit involving relay cells of the lateral geniculate nucleus and cells of the perigeniculate nucleus (a part of the thalamic reticular nucleus): geniculate relay cells innervate the perigeniculate nucleus, which, in turn, provides an inhibitory, GABAergic projection back to the lateral geniculate nucleus. However, feedback inhibition at the single-cell level requires that a given perigeniculate cell project back onto the same geniculate relay cell that innervates it. We probed for this in an in vitro slice preparation of the cat's lateral geniculate nucleus. We evoked a single action potential in a geniculate cell via a brief, depolarizing pulse delivered through an intracellular recording electrode and looked for any evoked hyperpolarizations. For 6 of the 36 geniculate cells tested, we observed a long-lasting hyperpolarization after the action potential, and much of this was eliminated by application of bicuculline, suggesting synaptically activated inhibitory postsynaptic potentials. We interpreted this to be clear evidence that a given neuron may inhibit itself via circuitry mediating feedback inhibition in the cat's lateral geniculate nucleus.Shanghai Brain Research Institute, Shanghai, People's Republic of China 200031     

The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus

Summary In the mammalian visual system, the lateral geniculate nucleus is commonly thought to act merely as a relay for the transmission of visual information from the retina to the visual cortex, a relay without significant elaboration in receptive field properties or signal strength. However, many morphological and electrophysiological observations are at odds with this view. Only 10–20% of the synapses found on geniculate relay neurons are retinal in origin. Roughly half of all synapses derive from cells in layer VI of visual cortex; roughly one third are inhibitory and GABAergic, derived either from interneurons or from cells of the nearby perigeniculate nucleus. Most of the remaining synapses probably derive from cholinergic, noradrenergic, and serotonergic sites within the brainstem reticular formation. Moreover, recent biophysical studies have revealed several ionic currents present in virtually all thalamic neurons. One is a Ca²⁺-dependent K⁺ current underlying the afterhyperpolarization (or the I_AHP), which may last up to 100–200 ms following an action potential. Activation of the I_AHP leads to spike frequency adaptation in response to a sustained, suprathreshold input. Intracellular recordings from other neuronal preparations have shown that the I_AHP can be blocked by noradrenalin or acetylcholine, leading to an increased cellular excitability. Another ionic current results from a voltage- and time-dependent Ca²⁺ conductance that produces a low threshold spike. Activation of this conductance transforms a geniculate neuron from a state of faithful relay of information to one of bursting behavior that bears little relationship to the activity of its retinal afférents. We propose that state-dependent gating of geniculate relay cells, which may represent part of the neuronal substrate involved in certain forms of selective visual attention, can be effected through at least three different mechanisms: (1) conventional GABAergic inhibition, which is largely controlled via brainstem and cortical afferents through interneurons and perigeniculate cells; (2) the I_AHP, which is controlled via noradrenergic and cholinergic afferents from the brainstem reticular formation; and (3) the low threshold spike, which may be controlled by GABAergic inputs, cholinergic inputs, and/or the corticogeniculate input, although other possibilities also exist. Furthermore, it seems likely that gating functions involving the corticogeniculate pathway are suited to attentional processes within the visual domain (e.g., saccadic suppression), whereas brain-stem inputs seem more likely to have more global effects that switch attention between sensory systems. In any case, it is now abundantly clear that geniculate circuitry and the intrinsic electrophysiological properties of geniculate neurons are no longer compatible with the notion that the lateral geniculate nucleus serves as a simple relay.     

The inhibitory role of the visually responsive region of the thalamic reticular nucleus in the rat

Summary Two-shock inhibition, a feature of 98 of 100 P cells recorded in the dorsal lateral geniculate nucleus of the normal rat, was not observed in 91 of 140 geniculate cells after an electrolytic lesion had been made in the adjacent visually responsive thalamic reticular nucleus. Nine geniculate cells recorded both before and after a reticular lesion had their initial inhibition abolished or substantially reduced after the lesion. The reticular lesion eliminated the bursts of spikes which normally terminate periods of inhibition following electrical or photic stimulation but caused no other changes in receptive field organization of geniculate cells. We conclude that the visually responsive region of the thalamic reticular nucleus in the rat is responsible for the profound two-shock inhibition and for the post-inhibitory bursts which are normal properties of relay cells of the dorsal lateral geniculate nucleus.     

The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus

The intracellular effects of brainstem peribrachial stimulation on lateral geniculate neurons were investigated in the cat. Experiments were performed in cats under barbiturate or urethane anaesthesia and in non-anaesthetized deafferented animals. Most animals were pretreated with reserpine and were acutely deprived of their retinal and visual cortical inputs. Short trains of stimuli triggered a transient depolarization in most relay neurons (latency: 20-30 ms; duration: 200-300 ms). This depolarization could be interrupted by a short-duration unitary inhibitory postsynaptic potential. The depolarization increased with membrane hyperpolarization and was associated with an increase in membrane conductance. The inhibitory postsynaptic potential had an intrathalamic origin and likely resulted from parallel activation of intrageniculate interneurons. The above responses were largely enhanced in reserpinized cats and were completely abolished by small doses of barbiturates. Iontophoretic applications of the nicotinic blocker, hexamethonium, eliminated peribrachial-evoked discharges in these cells, while similar applications of the muscarinic antagonist, scopolamine, were devoid of any effect. The conclusion is reached that the depolarization of lateral geniculate relay neurons by peribrachial afferents represents a direct postsynaptic effect and does not result from a global disinhibitory mechanism involving inhibition of perigeniculate cells and intrageniculate interneurons. This peribrachial-evoked transient excitation of relay neurons results from a nicotinic mechanism.     

Intracellular recordings from binocularly activated cells in the cat's dorsal lateral geniculate nucleus

Five binocularly activated cells near the interlaminar layers of the dorsal lateral geniculate nucleus have been studied with intracellular recording techniques. Four neurons were relay cells and antidromically activated from the visual cortex. They received monosynaptic excitation and disynaptic inhibition from Y type retinal ganglion cells in both eyes and disynaptic recurrent inhibition. The fifth cell was similar to perigeniculate neurons. It received disynaptic excitation from retinal ganglion cells in both eyes and monosynaptic excitation from antidromically activated relay cell axons. It was also inhibited from all these sources after an additional synaptic delay. The cell had a large receptive field, about twice the center size of neighboring relay cells, and gave on-off responses from the entire response area. Such displaced perigeniculate like cells may explain why relay cells issue occasional axon collaterals within the dorsal lateral geniculate nucleus.     

Locus ceruleus and neuronal activity of the reticular nucleus of the thalamus

Reactions of neurons of the reticular nucleus of the thalamus and lateral geniculate body to stimulation of the locus ceruleus were studied on their unanesthesized, immobilized cats. It was found that preliminary brief rhythmic stimulation of the locus ceruleus causes inhibition of the activity of the majority of neurons of the reticular nucleus and facilitation of relay neurons of the lateral geniculate body. Such reactions are clearly exhibited during simultaneous recording (by means of two microelectrodes) of the neuronal acitvity of these brain structures.Translated from Fiziologicheskii Zhurnal SSSR, imeni I. M. Sechenova, Vol. 71, No. 1, pp. 15–21, January, 1985.     

Synaptic terminals in the dorsal lateral geniculate nucleus from neurons of the thalamic reticular nucleus: A light and electron microscope autoradiographic study

(³H)-proline was injected in the caudodorsal part (visual segment) of the thalamic reticular nucleus to study its projection to the dorsal lateral geniculate nucleus. This was done by autoradiographic tracing of anterograde axonal transport of tritium at the light- and electron microscopic level. The results of the light-microscope autoradiography show that connections of the thalamic reticular nucleus are distributed along lines of projections in the dorsal lateral geniculate nucleus, indicating a retinotopic arrangement of this projection. The results of the electron microscope autoradiography provide direct evidence that axons of cells in the thalamic reticular nucleus terminate in the dorsal lateral geniculate nucleus as synaptic boutons that contain flattened synaptic vesicles, dark mitochondria and establish symmetrical synapses with perikarya and with proximal, intermediate and distal dendrites. They do not take part in intraglomerular synapses (as boutons with pleomorphic synaptic vesicles do) and are not postsynaptic to other vesicle-containing boutons in the dorsal lateral geniculate nucleus.The present results, taken in conjunction with physiological studies that have shown postsynaptic inhibitory effects of the thalamic reticular nucleus on dorsal lateral geniculate nucleus relay cells in the rat, establish a correlation of an inhibitory synapse with the presence of flattened synaptic vesicles in the corresponding synaptic boutons. Also, the observation that thalamic reticular nucleus terminals in the dorsal lateral geniculate nucleus avoid forming synapses with boutons containing pleomorphic vesicles, believed to be synaptic processes of interneurons, is indicative that the inhibitory effects are exerted monosynaptically on geniculate relay cells.     

Organization of visual inputs to interneurons of lateral geniculate nucleus of the cat.

1. Two groups of interneurons that are involved in the organization of the lateral geniculate nucleus (LGN) are described. The cell bodies of one group lie within the LGN; these units are referred to as intrageniculate. The cell bodies of the other group are found immediately above the LGN at its border with the perigeniculate nucleus; these units are referred to as perigeniculate. 2. Intrageniculate interneurons have center-surround receptive fields that resemble those of relay (principal) cells. They can be subdivided into brisk or sluggish and sustained or transient categories. They are stimulated transsynaptically from the visual cortex and have a characteristic variation in the latency of their spike response to such stimulation both at threshold and for suprathreshold stimuli. The pathway for this stimulation appears to be via cortical efferents to the LGN. Intrageniculate interneurons receive direct, monosynaptic retinal inputs, as determined by recording simultaneously from such interneurons and from the ganglion cells which provide excitatory input to them. Similar to relay cells, they are shown to have one or two major ganglion cell inputs. 3. Perigeniculate interneurons are generally binocularly innervated and give on-off responses to small spot stimuli throughout their receptive field. They respond well to rapid movement of large targets. They respond to electrical stimulation of the retina with a spike latency that falls between that of brisk transient and brisk sustained relay cells. This latency is one synaptic delay longer than that of brisk transient relay cell activation and suggests that they are excited by axon collaterals of these relay cells. Electrical stimulation of the visual cortex is also consistent with this model; the latency of the response of perigeniculate interneurons is approximately one synaptic delay longer than the latency of the response of brisk transient relay cells. 4. The interneuronal pathways described are consistent with proposed circuits that subserve the generation of IPSPs that arise in response to optic nerve and visual cortical stimulation. We now show that such inhibition has feed-forward (intrageniculate) and feed-back (perigeniculate) components that are mediated by two different classes of geniculate interneurons. It is suggested that the intrageniculate interneurons are involved in precise, spatially organized inhibition and that the perigeniculate interneurons are part of a more general, diffuse inhibitory system that modulates LGN excitability.     

Location of interneurones in the recurrent inhibitory circuit of the rabbit lateral geniculate nucleus

Summary Injection of horseradish peroxidase (HRP) into the dorsal lateral geniculate nucleus (LGN) of the rabbit gave rise to retrograde labeling of neurones in the caudal part of the thalamic reticular nucleus. Electrophysiological observations demonstrated that these neurones met all criteria for interneurones in the recurrent inhibitory circuit of the geniculo-cortical pathway. They responded to stimulation of the visual cortex (Cx) or the optic chiasm (OX) with a burst of repetitive discharges, in agreement with the long-lasting IPSP from Cx or OX in relay cells of LGN. Results of collision test showed that the reticular neurones received excitatory input via axonal collaterals of relay cells. The latency of their response to stimulation of Cx or OX is about 1.8 ms shorter than that of the corresponding IPSP in the relay cells. Stimulation of LGN evoked an antidromic spike in reticular neurones with a latency of bout 1.1 ms, indicating a monosynaptic projection from the latter to the relay cells. All evidence indicates that interneurones in the recurrent inhibitory circuit are most likely located in the caudal part of the thalamic reticular nucleus of the rabbit.     

The effects of brainstem peribrachial stimulation on perigeniculate neurons: the blockage of spindle waves

The mode of action of afferents arising from the brainstem peribrachial region at the midbrain-pontine junction on neurons recorded from the reticular thalamic sector adjacent to the lateral geniculate nucleus (perigeniculate cells) was investigated at the intracellular level in the cat. Experiments were performed in cats under barbiturate or urethane anaesthesia and in non-anaesthetized deafferented animals. Most cats were pretreated with reserpine (1-2 mg/kg) and were also acutely deprived of their retinal and cortical visual inputs. It was found that peribrachial stimulation produced a short train of fast-rising depolarizations followed by a long-lasting period of hyperpolarization in all perigeniculate neurons. Although the latest part of the early depolarizations preceding the hyperpolarization resulted from a parallel activation of lateral geniculate relay neurons by peribrachial afferents, those occurring at shortest latencies appear to result from a direct excitation produced by peribrachial afferents. Furthermore, these early excitatory postsynaptic potentials persisted under deep barbiturate anaesthesia, a condition that prevents activation of thalamic relay neurons by peribrachial stimulation. The evoked hyperpolarization decreased with membrane hyperpolarization, was associated with a 40-50% increase in membrane conductance and was insensitive to Cl injections. It was no longer observed within one hour after i.v. injection of scopolamine. However, the depolarizing responses were not depressed by this muscarinic antagonist. Iontophoretic applications of scopolamine also removed peribrachial-evoked inhibition of synaptic responses triggered by optic chiasma stimulation. The peribrachial input exerted a powerful control on the oscillatory behavior of perigeniculate neurons. Spindle oscillations which are generated within the reticular thalamic complex were readily blocked by peribrachial stimulation. It is then concluded that the transition from an oscillatory to a relay mode of operation in the thalamus is controlled at least in part by a muscarinic inhibition of reticular thalamic neurons. The synaptic mechanism responsible for the early depolarization remains to be elucidated.