Integration of signals from different cortical areas in higher order thalamic neurons

Higher order thalamic neurons receive driving inputs from cortical layer 5 and project back to the cortex, reflecting a transthalamic route for corticocortical communication. To determine whether or not individual neurons integrate signals from different cortical populations, we combined electron microscopy “connectomics” in mice with genetic labeling to disambiguate layer 5 synapses from somatosensory and motor cortices to the higher order thalamic posterior medial nucleus. A significant convergence of these inputs was found on 19 of 33 reconstructed thalamic cells, and as a population, the layer 5 synapses were larger and located more proximally on dendrites than were unlabeled synapses. Thus, many or most of these thalamic neurons do not simply relay afferent information but instead integrate signals as disparate in this case as those emanating from sensory and motor cortices. These findings add further depth and complexity to the role of the higher order thalamus in overall cortical functioning.

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Responses of thalamic neurons to itch- and pain-producing stimuli in rats

Journal of Neurophysiology ◽

10.1152/jn.00264.2018 ◽

2018 ◽

Vol 120 (3) ◽

pp. 1119-1134 ◽

Cited By ~ 6

Author(s):

Brett Lipshetz ◽

Sergey G. Khasabov ◽

Hai Truong ◽

Theoden I. Netoff ◽

Donald A. Simone ◽

...

Keyword(s):

Single Unit ◽

Electrophysiological Study ◽

Receptive Fields ◽

The Body ◽

Cell Column ◽

Thalamic Neurons ◽

Medial Nucleus ◽

Anesthetized Rats ◽

Transmission Of Information ◽

Posterior Medial Nucleus

Understanding of processing and transmission of information related to itch and pain in the thalamus is incomplete. In fact, no single unit studies of pruriceptive transmission in the thalamus have yet appeared. In urethane-anesthetized rats, we examined responses of 66 thalamic neurons to itch- and pain- inducing stimuli including chloroquine, serotonin, β-alanine, histamine, and capsaicin. Eighty percent of all cells were activated by intradermal injections of one or more pruritogens. Forty percent of tested neurons responded to injection of three, four, or even five agents. Almost half of the examined neurons had mechanically defined receptive fields that extended onto distant areas of the body. Pruriceptive neurons were located within what appeared to be a continuous cell column extending from the posterior triangular nucleus (PoT) caudally to the ventral posterior medial nucleus (VPM) rostrally. All neurons tested within PoT were found to be pruriceptive. In addition, neurons in this nucleus responded at higher frequencies than did those in VPM, an indication that PoT might prove to be a particularly interesting region for additional studies of itch transmission. NEW & NOTEWORTHY Processing of information related to itch within in the thalamus is not well understood, We show in this, the first single-unit electrophysiological study of responses of thalamic neurons to pruritogens, that itch-responsive neurons are concentrated in two nuclei within the rat thalamus, the posterior triangular, and the ventral posterior medial nuclei.

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Target-specific M1 inputs to infragranular S1 pyramidal neurons

Journal of Neurophysiology ◽

10.1152/jn.01032.2015 ◽

2016 ◽

Vol 116 (3) ◽

pp. 1261-1274 ◽

Cited By ~ 11

Author(s):

Amanda K. Kinnischtzke ◽

Erika E. Fanselow ◽

Daniel J. Simons

Keyword(s):

Primary Motor Cortex ◽

Pyramidal Neurons ◽

Projection Neurons ◽

Cell Type ◽

Intrinsic Properties ◽

Subcortical Structures ◽

Medial Nucleus ◽

Cell Type Specific ◽

Posterior Medial Nucleus

The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures.

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Differences in Response to Muscarinic Activation Between First and Higher Order Thalamic Relays

Journal of Neurophysiology ◽

10.1152/jn.00578.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3538-3547 ◽

Cited By ~ 29

Author(s):

C. Varela ◽

S. Murray Sherman

Keyword(s):

Brain Slices ◽

Medial Geniculate Body ◽

Input Resistance ◽

Higher Order ◽

First Order ◽

Medial Nucleus ◽

Dorsal Portion ◽

Medial Geniculate ◽

Lateral Posterior ◽

Posterior Medial Nucleus

The mammalian thalamus is composed of two types of thalamocortical relay. First order relays receive information from subcortical sources and relay it to cortex, whereas higher order relays receive information from layer 5 of one cortical area and relay it to another. Recent reports suggest that modulatory inputs to first and higher order relays may differ. We used rat thalamic brain slices and whole cell recordings from relay cells in various first order (the lateral geniculate nucleus, the ventral posterior nucleus, and the ventral portion of the medial geniculate body) and higher order (the lateral posterior, the posterior medial nucleus, and the dorsal portion of the medial geniculate body) relays to explore their responses to activation of muscarinic receptors. We found that, whereas all first order relay cells show a depolarizing response to muscarinic activation, ∼20% of higher order relay cells respond with hyperpolarization. The depolarization is accompanied by an overall increase in input resistance, whereas the hyperpolarization correlates with a decrease in resistance. Because activation of cholinergic brain stem afferents to thalamus increases with increasing behavioral vigilance, the findings suggest that increased vigilance will depolarize all first order and most higher order relay cells but will hyperpolarize a significant subset of higher order relay cells. Such hyperpolarization is expected to bias these relay cells to the burst firing mode, and so these results are consistent with evidence of more bursting among higher order than first order relay cells.

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Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function

PLoS ONE ◽

10.1371/journal.pone.0148169 ◽

2016 ◽

Vol 11 (1) ◽

pp. e0148169 ◽

Cited By ~ 22

Author(s):

Carlos Castejon ◽

Natali Barros-Zulaica ◽

Angel Nuñez

Keyword(s):

Cortical Processing ◽

Cortical Function ◽

Medial Nucleus ◽

Posterior Medial Nucleus

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Somatosensory Corticothalamic Projections: Distinguishing Drivers From Modulators

Journal of Neurophysiology ◽

10.1152/jn.00322.2004 ◽

2004 ◽

Vol 92 (4) ◽

pp. 2185-2197 ◽

Cited By ~ 154

Author(s):

Iva Reichova ◽

S. Murray Sherman

Keyword(s):

Lateral Geniculate Nucleus ◽

Ampa Receptor ◽

Metabotropic Glutamate Receptor ◽

Cortical Layer ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Medial Nucleus ◽

Lateral Geniculate ◽

Posterior Medial Nucleus ◽

Paired Pulse Depression

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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Organization and somatotopy of corticothalamic projections from L5B in mouse barrel cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1704302114 ◽

2017 ◽

Vol 114 (33) ◽

pp. 8853-8858 ◽

Cited By ~ 12

Author(s):

Anton Sumser ◽

Rebecca A. Mease ◽

Bert Sakmann ◽

Alexander Groh

Keyword(s):

Spatial Organization ◽

Barrel Cortex ◽

Cortical Layer ◽

Three Dimensions ◽

Zona Incerta ◽

Medial Nucleus ◽

Posterior Group ◽

Posterior Medial Nucleus ◽

Whisker Map ◽

Corticothalamic Projections

Neurons in cortical layer 5B (L5B) connect the cortex to numerous subcortical areas. Possibly the best-studied L5B cortico–subcortical connection is that between L5B neurons in the rodent barrel cortex (BC) and the posterior medial nucleus of the thalamus (POm). However, the spatial organization of L5B giant boutons in the POm and other subcortical targets is not known, and therefore it is unclear if this descending pathway retains somatotopy, i.e., body map organization, a hallmark of the ascending somatosensory pathway. We investigated the organization of the descending L5B pathway from the BC by dual-color anterograde labeling. We reconstructed and quantified the bouton clouds originating from adjacent L5B columns in the BC in three dimensions. L5B cells target six nuclei in the anterior midbrain and thalamus, including the posterior thalamus, the zona incerta, and the anterior pretectum. The L5B subcortical innervation is target specific in terms of bouton numbers, density, and projection volume. Common to all target nuclei investigated here is the maintenance of projection topology from different barrel columns in the BC, albeit with target-specific precision. We estimated low cortico–subcortical convergence and divergence, demonstrating that the L5B corticothalamic pathway is sparse and highly parallelized. Finally, the spatial organization of boutons and whisker map organization revealed the subdivision of the posterior group of the thalamus into four subnuclei (anterior, lateral, medial, and posterior). In conclusion, corticofugal L5B neurons establish a widespread cortico–subcortical network via sparse and somatotopically organized parallel pathways.

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ANDROST-5-ENE-3β,17β-DIOL IN OVARY OF POST-MENOPAUSAL HYPEROESTROGENIC WOMEN

Acta Endocrinologica ◽

10.1530/acta.0.0580364 ◽

1968 ◽

Vol 58 (3) ◽

pp. 364-376 ◽

Cited By ~ 5

Author(s):

S. Pesonen ◽

M. Ikonen ◽

B-J. Procopé ◽

A. Saure

Keyword(s):

Ovarian Tissue ◽

Cortical Layer ◽

Vaginal Smears ◽

Incubation Experiments ◽

Cell Groups ◽

Post Menopause ◽

Reducing Activity ◽

Post Menopausal ◽

One Year

ABSTRACT The ovaries of ten patients, at least one year after the post-menopause, were incubated with two Δ5-C19-steroids and also studied histochemically. All these patients had post-menopausal uterine bleeding and increased oestrogen excretion of the urine. The urinary estimations of gonadotrophins, 17-KS, 17-OHCS and pregnanediol were carried out on all patients. Vaginal smears were read according to Papanicolaou, and the endometrium and ovaries were studied histologically. The incubation experiments indicate the presence of Δ5-3β-hydroxysteroid-dehydrogenase. When androst-5-ene-3β,17β-diol was used as precursor the formation of testosterone occurred without any concomitant production of DHA and/or androstenedione. This seems to indicate the possible role of the Δ5-pathway in the formation of testosterone by post-menopausal ovarian tissue. The histochemical reactions indicated a reducing activity on NADH, lactate and glucose-6-phosphate, in certain corpora albicantia, atretic follicles and in diffuse thecoma regions in the cortical layer of the ovary. Steroid-3β-ol-dehydrogenase and β-hydroxybutyrate-dehydrogenase were found only at the edges of certain corpora albicantia, in some individual stroma cell groups and in some atretic follicles. Our studies, both biochemical and histochemical, suggest that the observed increase in the urinary oestrogens of the patients studied might in part at least, be of ovarian origin. This opinion is also supported by the postoperative oestrogen values.

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Subcortical circuits mediate communication between primary sensory cortical areas in mice

Nature Communications ◽

10.1038/s41467-021-24200-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Michael Lohse ◽

Johannes C. Dahmen ◽

Victoria M. Bajo ◽

Andrew J. King

Keyword(s):

Cortical Neurons ◽

Common Property ◽

Primary Auditory Cortex ◽

Facilitatory Effect ◽

Thalamic Nuclei ◽

Auditory Midbrain ◽

Cortical Areas ◽

Auditory Responses ◽

Evoked Activity

AbstractIntegration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.

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