The multifaceted role of inhibitory interneurons in the dorsal lateral geniculate nucleus

Intrinsic interneurons within the dorsal lateral geniculate nucleus (dLGN) provide a feed-forward inhibitory pathway for afferent visual information originating from the retina. These interneurons are unique because in addition to traditional axodendritic output onto thalamocortical neurons, these interneurons have presynaptic dendrites that form dendrodendritic synapses onto thalamocortical neurons as well. These presynaptic dendrites, termed F2 terminals, are tightly coupled to the retinogeniculate afferents that synapse onto thalamocortical relay neurons. Retinogeniculate stimulation of F2 terminals can occur through the activation of ionotropic and/or metabotropic glutamate receptors. The stimulation of ionotropic glutamate receptors can occur with single stimuli and produces a short-lasting inhibition of the thalamocortical neuron. By contrast, activation of metabotropic glutamate receptors requires tetanic activation and results in longer-lasting inhibition in the thalamocortical neuron. The F2 terminals are predominantly localized to the distal dendrites of interneurons, and the excitation and output of F2 terminals can occur independent of somatic activity within the interneuron thereby allowing these F2 terminals to serve as independent processors, giving rise to focal inhibition. By contrast, strong transient depolarizations at the soma can initiate a backpropagating calcium-mediated potential that invades the dendritic arbor activating F2 terminals and leading to a global form of inhibition. These distinct types of output, focal versus global, could play an important role in the temporal and spatial roles of inhibition that in turn impacts thalamocortical information processing.

Thalamic microcircuits: presynaptic dendrites form two feedforward inhibitory pathways in thalamus

In the visual thalamus, retinal afferents activate both local interneurons and excitatory thalamocortical relay neurons, leading to robust feedforward inhibition that regulates the transmission of sensory information from retina to neocortex. Peculiarly, this feedforward inhibitory pathway is dominated by presynaptic dendrites. Previous work has shown that the output of dendritic terminals of interneurons, also known as F2 terminals, are regulated by both ionotropic and metabotropic glutamate receptors. However, it is unclear whether both classes of glutamate receptors regulate output from the same or distinct dendritic terminals. Here, we used focal glutamate uncaging and whole cell recordings to reveal two types of F2 responses in rat visual thalamus. The first response, which we are calling a Type-A response, was mediated exclusively by ionotropic glutamate receptors (i.e., AMPA and NMDA). In contrast, the second response, which we are calling a Type-B response, was mediated by a combination of ionotropic and type 5 metabotropic glutamate receptors (i.e., mGluR5). In addition, we demonstrate that both F2 responses are evoked in the same postsynaptic neurons, which are morphologically distinct from neurons in which no F2 responses are observed. Since photostimulation was relatively focal and small in magnitude, these results suggest distinct F2 terminals, or small clusters of terminals, could be responsible for generating the two inhibitory responses observed. Because of the nature of ionotropic and metabotropic glutamate receptors, we predict the efficacy by which the retina communicates with the thalamus would be strongly regulated by 1) the activity level of a given retinogeniculate axon, and 2) the specific type of F2 terminals activated.

The NMDAR1 subunit of the N-methyl-D-aspartate receptor is localized at postsynaptic sites opposite both retinal and cortical terminals in the cat superior colliculus

The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor that is important in neurotransmission as well as in processes of synaptic plasticity in the mammalian superior colliculus (SC). Despite the importance of this receptor in synaptic transmission, there is as yet no evidence that demonstrates directly the synaptic localization of the NMDAR receptor in SC. We have used electron-microscope (EM) immunocytochemistry to localize the NMDAR1 subunit of this receptor protein and its association with sensory afferents in the cat SC. Retinal synaptic terminals were identified by normal morphology and cortical synaptic terminals by degeneration after lesions of areas 17–18 of the visual cortex. At the light-microscope level, label was densest within the superficial gray and upper optic layers, but also present in all other layers. Label was contained within cell bodies, dendrites, and a few putative axons. At the EM level, antibody labeling was found along postsynaptic densifications and internalized within the cytoplasm of a variety of dendrites and some cell bodies. Postsynaptic profiles labeled by NMDAR1 included conventional dendrites and presynaptic dendrites which contained pleomorphic synaptic vesicles and are known to be GABAergic. Many of the labeled postsynaptic densifications of both of these profile types received synaptic inputs from retinal or cortical terminals. Virtually no NMDAR1 immunoreactivity was found on thin dendritic thorns or putative spines, even when these were postsynaptic to retinal or cortical terminals. In summary, these results show that the NMDAR1 subunit is postsynaptic to both retinal and cortical afferents, which are known to be glutamatergic, and are consistent with physiological evidence showing that stimulation of either pathway can activate the NMDA receptor.

Three types of inhibitory postsynaptic potentials generated by interneurons in the anterior thalamic complex of cat

1. These experiments were carried out to study how thalamic interneurons generate inhibitory postsynaptic potentials (IPSPs) in relay cells. Intracellular recordings were performed in the anterior thalamic (AT) nuclei, a nuclear group in which interneurons constitute the only intrathalamic source of gamma-aminobutyric acid (GABA). 2. In the AT complex, as in most dorsal thalamic nuclei, interneurons can influence relay cells through their presynaptic dendrites (PSDs) and their axons. This dual mode of action is paralleled by a different termination pattern of prethalamic fibers and cortical axons on interneurons. Prethalamic fibers, which in the AT nuclei arise in the mammillary bodies (MBs), end mostly on PSDs, whereas cortical terminals usually synapse on the parent dendrites of PSDs. We therefore took advantage of the differential mode of termination of cortical and MB afferents on interneurons to infer the respective roles of the axons and PSDs of interneurons in the genesis of the IPSPs recorded from relay cells. 3. In all responsive AT cells, cortical stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a biphasic IPSP, with an early and a late phase, having a total duration of 221.96 +/- 8.18 ms (mean +/- SE). The early part of the IPSP (termed A) had a reversal potential (ER) close to the equilibrium potential for Cl- ions: -79.25 +/- 2.14 mV. Furthermore, it reversed in polarity after impalement of the cells with KCl-filled pipettes. The late IPSP (termed B) always began before the end of the early IPSP, 45.93 +/- 2.50 ms after the onset of the A-IPSP. The B-IPSP had an ER of -109 +/- 2.4 mV and was not affected by Cl- injection. 4. By contrast, MB stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a triphasic IPSP having a total duration of 220.5 +/- 9.42 ms in most (61.2%) AT cells. The IPSP with the shortest latency (termed a) was evoked only by MB stimuli. Before the return of the membrane potential to the resting level, a second hyperpolarizing potential began (7.41 +/- 0.46 ms after the onset of the a-IPSP). This second inhibitory phase was biphasic and had electrophysiological characteristics similar to the biphasic A- and B-IPSP evoked by cortical stimulation. Both the MB-evoked a- and A-IPSPs had an ER close to the equilibrium potential for Cl- ions (-72.22 +/- 0.68 and -72 +/- 0.82 mV, respectively) and reversed in polarity after impalement of the cells with KCl-filled pipettes.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphology of physiologically characterized medial lemniscal axons terminating in cat ventral posterior thalamic nucleus

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.