Extended Data Fig. 7: The DCN supplies high force information to the middle VPL (mVPL).

The primary somatosensory thalamus can be subdivided into rostral, middle and caudal regions⁵⁷. Rostral regions may receive more proprioceptive input and have large receptive fields. The middle region has cutaneous responses with detailed spatial receptive fields. The caudal region has diffuse receptive fields and may be more responsive to intense nociceptive stimuli. We asked whether the mVPL can encode the intensity of sustained stimuli, and whether such coding arises from the anterolateral tract (ALT) or the dorsal column system. We recorded from the mVPL in urethane-anesthetized mice and lesioned the DCN to measure how mechanically-evoked responses change. The dorsal column system crosses just rostral to the DCN, whereas the ALT crosses within the spinal cord and runs laterally. Other spinothalamic and ascending neurons also cross within the spinal cord and run along the ventral aspect of the brainstem, and should be spared by lesioning the DCN. However, a potential caveat is that lesioning the DCN may disrupt the descending corticospinal tract, which passes just ventrally to the DCN toward the spinal cord. a, Schematized experimental configuration. A 32-channel multi-electrode array (MEA) was inserted into the middle VPL of the right thalamus. Mechanical indentation of the contralateral (left) hindpaw was performed before and after lesion of the left DCN by aspiration. The lesion should disrupt DCN input from reaching the VPL, but spare input from ALT neurons. b, Coronal section of the brain (50 µm) following recording with DiI labeling from the MEA in the right VPL (top). Scale bar is 1 mm. Inset shows magnified view of the thalamus (bottom left) and inferred location of VPL and thalamic reticular nucleus (Rt, bottom right). Scale bar is 1 mm (top) and 100 µm (bottom). Histological verification of the electrode track was performed in one animal. c, Coronal section of the brainstem showing the location of the lesion. The dorsal brainstem was aspirated at the level of the caudal DCN on the left side (top). Inset shows magnified view of the lesion site, and location of the gracile nucleus (GrN) that relays information from the hindpaw, and also the cuneate tract (cu) and some of the cuneate nucleus (CuN). Scale bar is 1 mm (top) and 200 µm (bottom). Histological verification of the lesion was performed in two animals.d, Waveform for a unit recorded across four channels of the MEA prior to the DCN lesion with a subset of single events (gray) and overlaid average (black). e, Autocorrelogram for unit shown in d–o prior to the lesion. f, Raster of firing for unit shown in d–o in response to a 300 ms step indentation of varying force. Trials were interleaved, but are shown sorted for presentation. g, Maximum firing rate for the onset of step indentation (0–50 ms) as a function of indentation force for unit shown in d–o prior to lesion. Dashed green line indicates the measured threshold. h, Average firing rate during the sustained component of the step indentation (150–300 ms) for unit shown in d–o prior to lesion as a function of force. i, Time course of firing rate for unit shown in d–o in response to indentation for 10 mN (top) and 250 mN (bottom) prior to lesion. j–o, Same as d–i, but for the same unit after DCN lesion. p, Average histograms for all mVPL units in response to 10 mN 300 ms indentation prior to lesion (left) and for the same units after DCN lesion (right). Units are sorted by strength of on-response to 10 mN indentation. q, Mean ± s.e.m of all mVPL units in response to 10 mN indentation before (left) and after (right) lesion of the DCN.r, Average histograms for all mVPL units in response to 250 mN 300 ms indentation prior to lesion (left) and for the same units after DCN lesion (right). Units are same as shown in p, but sorted by strength of sustained response at 250 mN. s, Mean ± s.e.m. of all mVPL units in response to 250 mN indentation before (left) and after (right) lesion of the DCN. t, Cumulative histogram of on-response threshold for the same units before (black) and after (red) lesion of the DCN. About 60% of units could no longer be activated by indentations up to 300 mN following DCN lesion. Kolmogorov-Smirnov test, p < 0.001. u, Mean ± s.e.m. of sustained response of all units as a function of indentation force before (black) and after (red) lesion of the DCN. Kolmogorov-Smirnov test, p < 0.001. v, Cumulative histogram of spontaneous firing rates for same units before (black) and after (red) lesion of the DCN. Kolmogorov-Smirnov test, p = 0.001. Data shown as n units in N animals (n/N).

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