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S Murray Sherman

Publications and source records attributed to S Murray Sherman.

15 recordsLinked to original sources
PubMed2006

An argument for an olfactory thalamus.

The mammalian olfactory system is unique in that sensory receptors synapse directly into the olfactory bulb of the forebrain without the thalamic relay that is common to all other sensory pathways. We argue that the olfactory bulb has an equivalent role to the thalamus, because the two regions have very similar structures and functions. Both the thalamus and the olfactory bulb are the final stage in sensory processing before reaching target cortical regions, at which there is a massive increase in neuron and synapse numbers. Thus, both structures act as a bottleneck that is a target for various modulatory inputs, and this arrangement enables efficient control of information flow before cortical processing occurs.

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PubMed2006

Mapping of the functional interconnections between thalamic reticular neurons using photostimulation.

The thalamic reticular nucleus is strategically located in the axonal pathways between thalamus and cortex, and reticular cells exert strong, topographic inhibition on thalamic relay cells. Although evidence exists that reticular neurons are interconnected through conventional and electrical synapses, the spatial extent and relative strength of these synapses are unclear. To address these issues, we used uncaging of glutamate by laser-scanning photostimulation to provide precisely localized and consistent activation of reticular cell bodies and dendrites in an in vitro slice preparation from the rat as a means to study reticulo-reticular connections. Among the 47 recorded reticular neurons, 29 (62%) received GABAergic axodendritic input from an area immediately surrounding each of the recorded cell bodies, and 8 (17%) responded with depolarizing spikelets, suggesting inputs through electrical synapses. We also found that TTX completely blocked all evoked IPSCs, implying that any dendrodendritic synapses between reticular cells either are relatively weak, have no nearby glutamatergic receptors, or are dependent on back-propagation of action potentials. Finally, we showed that the GABAergic connections between reticular cells are weaker than those from reticular cells to relay cells. Our results suggest that the GABAergic axodendritic synapse is the dominant form of reticulo-reticular connectivity, and because they are much weaker than the reticulo-relay cell synapses, their functional purpose may be to regulate the spatial extent of the reticular inhibition on relay cells.

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PubMed2005

Thalamic relays and cortical functioning.

Studies on the visual thalamic relays, the lateral geniculate nucleus and pulvinar, provide three key properties that have dramatically changed the view that the thalamus serves as a simple relay to get information from subcortical sites to cortex. First, the retinal input, although a small minority (7%) in terms of numbers of synapses onto geniculate relay cells, dominates receptive field properties of these relay cells and strongly drives them; 93% of input thus is nonretinal and modulates the relay in dynamic and important ways related to behavioral state, including attention. We call the retinal input the driver input and the nonretinal, modulator input, and their unique morphological and functional differences allow us to recognize driver and modulator input to many other thalamic relays. Second, much of the modulation is related to control of a voltage-gated, low threshold Ca(2+) conductance that determines response properties of relay cells -burst or tonic - and this, among other things, affects the salience of information relayed. Third, the lateral geniculate nucleus and pulvinar (a massive but generally mysterious and ignored thalamic relay), are examples of two different types of relay: the LGN is a first order relay, transmitting information from a subcortical driver source (retina), while the pulvinar is mostly a higher order relay, transmitting information from a driver source emanating from layer 5 of one cortical area to another area. Higher order relays seem especially important to general corticocortical communication, and this view challenges the conventional dogma that such communication is based on direct corticocortical connections. In this sense, any new information reaching a cortical area, whether from a subcortical source or another cortical area, benefits from a thalamic relay. Other examples of first and higher order relays also exist, and generally higher order relays represent the majority of thalamus. A final property of interest emphasized in chapter 17 by Guillery (2005) is that most or all driver inputs to thalamus, whether from a subcortical source or from layer 5 of cortex, are axons that branch, with the extrathalamic branch innervating a motor or premotor region in the brainstem, or in some cases, spinal cord. This suggests that actual information relayed by thalamus to cortex is actually a copy of motor instructions (Guillery, 2005). Overall, these features of thalamic relays indicate that the thalamus not only provides a behaviorally relevant, dynamic control over the nature of information relayed, it also plays a key role in basic corticocortical communication.

Action Potentials↗
PubMed2005

Mapping by laser photostimulation of connections between the thalamic reticular and ventral posterior lateral nuclei in the rat.

We used laser scanning photostimulation through a focused UV laser of caged glutamate in an in vitro slice preparation through the rat's somatosensory thalamus to study topography and connectivity between the thalamic reticular nucleus and ventral posterior lateral nucleus. This enabled us to focally stimulate the soma or dendrites of reticular neurons. We were thus able to confirm and extend previous observations based mainly on neuroanatomical pathway tracing techniques: the projections from the thalamic reticular nucleus to the ventral posterior lateral nucleus have precise topography. The reticular zone, which we refer to as a "footprint," within which photostimulation evoked inhibitory postsynaptic currents (IPSCs) in relay cells, was relatively small and oval, with the long axis being parallel to the border between the thalamic reticular nucleus and ventral posterior lateral nucleus. These evoked IPSCs were large, and by using appropriate GABA antagonists, we were able to show both GABA(A) and GABA(B) components. This suggests that photostimulation strongly activated reticular neurons. Finally, we were able to activate a disynaptic relay cell-to-reticular-to- relay cell pathway by evoking IPSCs in relay cells from photostimulation of the region surrounding a recorded relay cell. This, too, suggests strong responses of relay cells, responses strong enough to evoke spiking in their postsynaptic reticular targets. The regions of photostimulation for these disynaptic responses were much larger than the above-mentioned reticular footprints, and this suggests that reticulothalamic axon arbors are less widespread than thalamoreticular arbors, that there is more convergence in thalamoreticular connections than in reticulothalamic connections, or both.

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PubMed2005

Morphological correlates of triadic circuitry in the lateral geniculate nucleus of cats and rats.

We used an in vitro slice preparation of the lateral geniculate nucleus in cats and rats to study morphological correlates of triadic circuitry in relay cells. The three triadic elements involve a retinal synapse onto a GABAergic dendritic terminal of an interneuron, a synapse from the same retinal terminal onto a relay cell dendrite, and a synapse from the same interneuron terminal onto the same relay cell dendrite. We made whole cell recordings and labeled cells with biocytin. Previous methods were used to identify triadic circuitry based on evidence that the retinal terminal activates a metabotropic glutamate receptor on the interneuronal terminal. Thus application of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (an agonist to that receptor) increases the rate of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in the relay cell, and if some of this increase remains with further addition of TTX (a TTX-insensitive response), a triad is indicated. We quantified the extent of the TTX-insensitive response and sought morphological correlates. In both rats and cats, this response correlated (negatively) with the number of primary dendrites and (positively) with polarity of the dendritic arbor. There was no correlation with cell size. Curiously, in cats, this response correlated with the presence of appendages at primary dendritic branches, but there was no such correlation in rats. These observations in cats map onto the X/Y classification, with X cells having triads, but it is not clear from our results if a comparable classification exists for rats.

Action Potentials↗
PubMed2004

Differences in projection patterns between large and small corticothalamic terminals.

We injected tracer into wide regions of visual cortex in the cat to produce retrograde and orthograde labeling in the thalamus, chiefly in the lateral geniculate nucleus and lateral posterior-pulvinar complex (LP-Pulvinar). We used the electron microscope to measure the sizes of orthogradely labeled terminals in thalamus and used these measurements to help determine whether the terminals were "RL" (large, presumed excitatory) or "RS" (small, presumed excitatory). We also distinguished reciprocal regions, which were zones of corticothalamic feedback defined by the presence of many retrogradely labeled cell bodies and orthogradely labeled terminals, from nonreciprocal regions, which were zones of feedforward corticothalamic projections defined by the presence of orthogradely labeled terminals alone. The lateral geniculate nucleus, a reciprocal region, had retrogradely labeled cell bodies as well as labeled RS terminals. Likewise, reciprocal regions in LP-Pulvinar were dominated by labeled RS terminals. In contrast, nonreciprocal regions were dominated by labeled RL terminals. Based on other evidence of corticothalamic projections that RL and RS terminals derive, respectively, from layer 5 and layer 6, we suggest the same relationship here, leading to the conclusion that the corticothalamic input from layer 6 is largely feedback, whereas that from layer 5 is largely feedforward. This finding lends credence to a recent hypothesis that layer 5 corticothalamic axons represent the afferent limb of a cortico-thalamo-cortical pathway that is critical for corticocortical communication.

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PubMed2004

Somatosensory corticothalamic projections: distinguishing drivers from modulators.

We used a juvenile mouse thalamocortical slice preparation with whole cell recording to investigate synaptic properties of corticothalamic inputs from somatosensory cortex to the ventral posterior medial and posterior medial nuclei (98 cells). We compared these data to those obtained from activating retinal and cortical inputs to the lateral geniculate nucleus (8 cells), the former representing a prototypical driver input and the latter, a typical modulator. Retinogeniculate activation evoked large, all-or-none excitatory postsynaptic potentials (EPSPs) that showed paired-pulse depression antagonized by N-methyl-d-aspartate (NMDA) and AMPA receptor blockers but with no sign of a metabotropic glutamate receptor (mGluR) component. Corticogeniculate activation evoked small, graded EPSPs showing paired-pulse facilitation, and the EPSPs showed both NMDA and AMPA receptor component plus an mGluR1 component. In the somatosensory thalamic relays, cortical stimulation elicited glutamatergic EPSPs in all thalamic cells, and these EPSPs fell into two groups. One, elicited from cortical layer 6 to cells of both nuclei, involved small, graded EPSPs with paired-pulse facilitation, and most also showed an mGluR1 component. The other, elicited from layer 5 to cells only of the posterior medial nucleus, involved large, all-or-none EPSPs with paired-pulse depression, and none showed an mGluR component. By analogy with results from the lateral geniculate nucleus, we conclude that the input from layer 6 to both nuclei acts as a modulator but that the layer 5 input to the posterior medial nucleus serves as a driver. Our data extend a common organizing principle from first-order nuclei to higher-order thalamic relays and further implicate the latter in corticocortical communication.

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PubMed2004

Interneurons and triadic circuitry of the thalamus.

The thalamus is strategically placed to control the flow of information to cortex and thus conscious perception. A key player in this control is a local GABAergic interneuron that inhibits relay cells. This interneuron is especially interesting because, in addition to a conventional axonal output, most of its output is via distal dendrites. The latter seem to be electrotonically and thus functionally isolated from the soma and axon, and they enter into complex synaptic arrangements. It is proposed that, because of special synaptic properties of its dendritic outputs, this local GABAergic interneuron of the thalamus provides gain control for the relay cell and thereby keeps relay of information to cortex within a fairly linear regime.

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PubMed2003

Functional synaptic contacts by intranuclear axon collaterals of thalamic relay neurons.

Relay neurons of the lateral geniculate nucleus innervate visual cortex, but they also provide axonal collaterals to neurons in the thalamic reticular nucleus, and these thalamic reticular neurons provide feedback inhibition to relay cells. An alternative source of inhibitory inputs onto geniculate relay neurons arises from intralaminar interneurons that provide feedforward inhibition via retinogeniculate innervation, and perhaps feedback inhibition via the corticothalamic pathway, analogous to that involving thalamic reticular neurons. Several reports indicate that relay neurons may also give rise to axonal collaterals within the lateral geniculate nucleus, constituting another route for feedback or local integration. We now provide new data indicating that collaterals from geniculate relay neurons provide excitatory input to local intralaminar interneurons and that this pathway may serve as a previously unknown means of local feedback inhibition. This circuitry could prove important in such activities as surround inhibition of receptive fields or increasing signal gain over noise.

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PubMed2003

Corticothalamic projections from the rat primary somatosensory cortex.

To study the cells of origin of corticothalamic inputs to the ventral posterior and posterior medial nuclei of the somatosensory thalamus in rats, we injected small aliquots of tracer into each nucleus and analyzed the pattern of retrograde labeling in the posteromedial barrel subfield of primary somatosensory cortex, which can be divided into barrel and nonbarrel zones. The ventral posterior nucleus is innervated by neurons in layer VIa of both zones, whereas the posterior medial nucleus is innervated by neurons in layers Vb and VIb of both zones with additional innervation from layer VIa of nonbarrel cortex. Thus, only the posterior medial nucleus receives a layer Vb input. Because the layer Vb input is interpreted as the initiation of a feedforward cortico-thalamocortical pathway, this implies that the target of the posterior medial nucleus, which includes the nonbarrel cortex, is a higher-order cortical area. We thus suggest that this cortical zone, which is classically considered part of the primary somatosensory cortex, should be reclassified as higher-order cortex.

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PubMed2003

Single-unit recording in the lateral geniculate nucleus of the awake behaving monkey.

In recent years, recording neuronal activity in the awake, behaving primate brain has become established as one of the major tools available to study the neuronal specificity of the initiation and control of various behaviors. Primates have traditionally been used in these studies because of their ability to perform more complex behaviors closely akin to those of humans, a desirable prerequisite since our ultimate aim is to elucidate the neuronal correlates of human behaviors. A wealth of knowledge has accumulated on the sensory and motor systems such as vision, audition, and eye movements. For more demanding behaviors where the main focus has been on attention, recordings in awake primates have begun to yield valuable data on the centers of the brain that are reactive to different attributes of this behavior. As a result, various hypotheses of the origin and distribution of attentional effects have evolved. For instance, visual attentional effects have been described not only in the higher cortical area (V4) but also in areas earlier in the visual pathway which presumably involve a feedback mechanism in the latter region. Here we outline the ways in which we have successfully used these methods to make single-cell recordings in awake macaques to show how certain behavioral paradigms affect neurons of the thalamus (with emphasis on the lateral geniculate nucleus). As we have done with established techniques these methods can be readily adapted to incorporate most behaviors needed to be tested and allow recordings to be made in virtually any part of the brain.

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PubMed2002

The role of the thalamus in the flow of information to the cortex.

The lateral geniculate nucleus is the best understood thalamic relay and serves as a model for all thalamic relays. Only 5-10% of the input to geniculate relay cells derives from the retina, which is the driving input. The rest is modulatory and derives from local inhibitory inputs, descending inputs from layer 6 of the visual cortex, and ascending inputs from the brainstem. These modulatory inputs control many features of retinogeniculate transmission. One such feature is the response mode, burst or tonic, of relay cells, which relates to the attentional demands at the moment. This response mode depends on membrane potential, which is controlled effectively by the modulator inputs. The lateral geniculate nucleus is a first-order relay, because it relays subcortical (i.e. retinal) information to the cortex for the first time. By contrast, the other main thalamic relay of visual information, the pulvinar region, is largely a higher-order relay, since much of it relays information from layer 5 of one cortical area to another. All thalamic relays receive a layer-6 modulatory input from cortex, but higher-order relays in addition receive a layer-5 driver input. Corticocortical processing may involve these corticothalamocortical 're-entry' routes to a far greater extent than previously appreciated. If so, the thalamus sits at an indispensable position for the modulation of messages involved in corticocortical processing.

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PubMed2002

Detectability of excitatory versus inhibitory drive in an integrate-and-fire-or-burst thalamocortical relay neuron model.

Although inhibitory inputs are often viewed as equal but opposite to excitatory inputs, excitatory inputs may alter the firing of postsynaptic cells more effectively than inhibitory inputs. This is because spike cancellation produced by an inhibitory input requires coincidence in time, whereas an excitatory input can add spikes with less temporal constraint. To test for such potential differences, especially in the context of the function of thalamocortical (TC) relay nuclei, we used a stochastic "integrate-and-fire-or-burst" TC neuron model to quantify the detectability of excitatory and inhibitory drive in the presence and absence of the low-threshold Ca2+ current, I(T), and the hyperpolarization-activated cation conductance, I(sag). We find that excitatory inputs are generally superior drivers compared with inhibitory inputs in part because spontaneous activity of a postsynaptic neuron is not required in the case of excitatory drive. Interestingly, the presence of the low-threshold Ca2+ current, I(T) in a postsynaptic neuron allows the robust detection of inhibitory drive over a certain range of spontaneous and driven activity, a range that can be extended by the presence of the hyperpolarization-activated cation conductance, I(sag). These simulations suggest a possible reinterpretation of the role of inhibitory inputs, such as those to the thalamus.

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PubMed2002

Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system.

All neocortical areas receive thalamic inputs. Some thalamocortical pathways relay information from ascending pathways (first order thalamic relays) and others relay information from other cortical areas (higher order thalamic relays), thus serving a role in corticocortical communication. Most, possibly all, afferents reaching thalamus, ascending and cortical, are branches of axons that innervate lower (motor) centers, so that thalamocortical pathways can be viewed generally as monitors of ongoing motor instructions. In terms of numbers, the thalamic relay is dominated by synapses that modulate the relay functions. One of the roles of these modulatory pathways is to change the transfer of information through the thalamus, in accord with current attentional demands. Other roles remain to be explored. These modulatory functions can be expected to act on corticocortical communication in addition to their action on ascending pathways.

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