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.

Progressive lacunar stroke presenting as cheiro-oral syndrome, dysarthria and hemiataxia

Context: Lacunar infarcts are small infarcts caused by occlusion of a single penetrating vessel, affecting mostly the basal ganglia, subcortical white matter and pons1. Around 20-30% of patients may progress symptoms over hours to days, and this presentation is associated with disability and poor prognosis2. Case report: A 70-year-old man with history of smoking, hypertension and a previous right occipital stroke reported right upper lip paresthesias since awakening. In 2-hours the right perioral region and his right hand were affected. After 3-hours he noted slurred speech. After 4-hours, imbalance was added to the previous symptoms. On admission, NIHSS was 4, mostly by previous left hemianopia, new right arm ataxia and cerebellar dysarthria. There were no weakness or sensory déficits. Brain MRI showed a subacute lacunar stroke in the left thalamus. Discussion: Thalamic lacunar strokes can present in a wide range of symptoms depending on the affected nuclei. The ventral posterior lateral nucleus (VPLn) and the ventral posterior medial nucleus (VPMn) carries sensory input from the contralateral body and face, respectively3. Cheiro-oral syndrome (COS) is considered a pure sensory thalamic lacunar syndrome with symptoms that affect the face, hand and/or foot, but may be accompanied by ipsilateral ataxia if the ventral lateral nucleus is also affected4 . Although classically associated with thalamic ischemic lesions, there are descriptions of hemorrhagic strokes5 and multiple different affected regions presenting as COS, including brainstem5 , internal capsule6 , operculum7 , cortex8 , corona radiata9 and thalamus10. Early recognition and diagnosis is essencial to institute adequate early treatment and secondary prophylaxis.

Synapses from the high-order thalamic nucleus and motor cortex are co-clustered in the distal tuft dendrites of the mouse somatosensory cortex

ABSTRACTThe posterior medial nucleus of the thalamus (POm) and vibrissal primary motor cortex (vM1) convey essential information to the barrel cortex (S1BF) regarding whisker position and movement. Therefore, understanding the relative spatial relationships of these two inputs is critical prerequisites to acquire insight into how S1 synthesizes information to interpret the location of an object. Using array tomography, we identified the locations of synapses from vM1 and POm on distal tuft dendrites of L5 pyramidal neurons. We found that synapses from vM1 and POm are spatially clustered on the same set of dendrites with unusually high density. Furthermore, the clusters of vM1 and POm synapses colocalize each other. These findings suggest that synaptic clusters, but not dendritic branches, act as functional units and cooperatively contribute to nonlinear dendritic responses.

High-order thalamic inputs to primary somatosensory cortex are stronger and longer lasting than cortical inputs

Layer (L) 2/3 pyramidal neurons in the primary somatosensory cortex (S1) are sparsely active, spontaneously and during sensory stimulation. Long-range inputs from higher areas may gate L2/3 activity. We investigated their in vivo impact by expressing channelrhodopsin in three main sources of feedback to rat S1: primary motor cortex, secondary somatosensory cortex, and secondary somatosensory thalamic nucleus (the posterior medial nucleus, POm). Inputs from cortical areas were relatively weak. POm, however, more robustly depolarized L2/3 cells and, when paired with peripheral stimulation, evoked action potentials. POm triggered not only a stronger fast-onset depolarization but also a delayed all-or-none persistent depolarization, lasting up to 1 s and exhibiting alpha/beta-range oscillations. Inactivating POm somata abolished persistent but not initial depolarization, indicating a recurrent circuit mechanism. We conclude that secondary thalamus can enhance L2/3 responsiveness over long periods. Such timescales could provide a potential modality-specific substrate for attention, working memory, and plasticity.

Unique properties of high-order thalamic inputs versus cortical inputs to primary somatosensory cortex

Layer (L) 2/3 pyramidal neurons in the primary somatosensory cortex (S1) are sparsely active, spontaneously and during sensory stimulation. Long-range inputs from higher areas may gate L2/3 activity. We investigated their in vivo impact by expressing channelrhodopsin in three main sources of feedback to rat S1: primary motor cortex, secondary somatosensory cortex, and secondary somatosensory thalamic nucleus (the posterior medial nucleus, POm). Inputs from cortical areas were relatively weak. POm, however, more robustly depolarized L2/3 cells and, when paired with peripheral stimulation, evoked action potentials. POm triggered not only a stronger fast-onset depolarization but also a delayed all-or-none persistent depolarization, lasting up to 1 second and exhibiting beta oscillations. Inactivating POm somata abolished persistent but not initial depolarization, indicating a recurrent circuit mechanism. We conclude that secondary thalamus can enhance L2/3 responsiveness over long periods. Such timescales could provide a potential modality-specific substrate for attention, working memory, and plasticity.

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

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.

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

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.