The Superior Colliculus/Lateral Posterior Thalamic Nuclei in Mice Rapidly Transmit Fear Visual Information Through the Theta Frequency Band.

Animals perceive threat information mainly from vision, and the subcortical visual pathway plays a critical role in the rapid processing of fear visual information. The superior colliculus (SC) and lateral posterior (LP) nuclei of the thalamus are key components of the subcortical visual pathway; however, how animals encode and transmit fear visual information is unclear. To evaluate the response characteristics of neurons in SC and LP thalamic nuclei under fear visual stimuli, extracellular action potentials (spikes) and local field potential (LFP) signals were recorded under looming and dimming visual stimuli. The results showed that both SC and LP thalamic nuclei were strongly responsive to looming visual stimuli but not sensitive to dimming visual stimuli. Under the looming visual stimulus, the theta (θ) frequency bands of both nuclei showed obvious oscillations, which markedly enhanced the synchronization between neurons. The functional network characteristics also indicated that the network connection density and information transmission efficiency were higher under fear visual stimuli. These findings suggest that both SC and LP thalamic nuclei can effectively identify threatening fear visual information and rapidly transmit it between nuclei through the θ frequency band. This discovery can provide a basis for subsequent coding and decoding studies in the subcortical visual pathways.

Response Selectivity of the Lateral Posterior Nucleus Axons Projecting to the Mouse Primary Visual Cortex.

Neurons in the mouse primary visual cortex (V1) exhibit characteristic response selectivity to visual stimuli, such as orientation, direction and spatial frequency selectivity. Since V1 receives thalamic visual inputs from the lateral geniculate nucleus (LGN) and lateral posterior nucleus (LPN), the response selectivity of the V1 neurons could be influenced mostly by these inputs. However, it remains unclear how these two thalamic inputs contribute to the response selectivity of the V1 neurons. In this study, we examined the orientation, direction and spatial frequency selectivity of the LPN axons projecting to V1 and compared their response selectivity with our previous results of the LGN axons in mice. For this purpose, the genetically encoded calcium indicator, GCaMP6s, was locally expressed in the LPN using the adeno-associated virus (AAV) infection method. Visual stimulations were presented, and axonal imaging was conducted in V1 by two-photon calcium imaging in vivo. We found that LPN axons primarily terminate in layers 1 and 5 and, to a lesser extent, in layers 2/3 and 4 of V1, while LGN axons mainly terminate in layer 4 and, to a lesser extent, in layers 1 and 2/3 of V1. LPN axons send highly orientation- and direction-selective inputs to all the examined layers in V1, whereas LGN axons send highly orientation- and direction-selective inputs to layers 1 and 2/3 but low orientation and direction selective inputs to layer 4 in V1. The distribution of preferred orientation and direction was strongly biased toward specific orientations and directions in LPN axons, while weakly biased to cardinal orientations and directions in LGN axons. In spatial frequency tuning, both the LPN and LGN axons send selective inputs to V1. The distribution of preferred spatial frequency was more diverse in the LPN axons than in the LGN axons. In conclusion, LPN inputs to V1 are functionally different from LGN inputs and may have different roles in the orientation, direction and spatial frequency tuning of the V1 neurons.

Visual intracortical and transthalamic pathways carry distinct information to cortical areas.

Sensory processing involves information flow between neocortical areas, assumed to rely on direct intracortical projections. However, cortical areas may also communicate indirectly via higher-order nuclei in the thalamus, such as the pulvinar or lateral posterior nucleus (LP) in the visual system of rodents. The fine-scale organization and function of these cortico-thalamo-cortical pathways remains unclear. We find that responses of mouse LP neurons projecting to higher visual areas likely derive from feedforward input from primary visual cortex (V1) combined with information from many cortical and subcortical areas, including superior colliculus. Signals from LP projections to different higher visual areas are tuned to specific features of visual stimuli and their locomotor context, distinct from the signals carried by direct intracortical projections from V1. Thus, visual transthalamic pathways are functionally specific to their cortical target, different from feedforward cortical pathways, and combine information from multiple brain regions, linking sensory signals with behavioral context.

Evidence for the role of the dorsal ventral lateral posterior thalamic nucleus connectivity in deep brain stimulation for Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) can manifest as debilitating, medically-refractory tics for which deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM) can provide effective treatment. However, patients have reported benefit with activation of contacts dorsal to the CM and likely in the ventro-lateral thalamus (VL). At our institution, a case of a robust and durable response in a GTS patient required stimulation in the CM and more dorsally. We explore the structural connectivity of thalamic subregions associated with GTS using diffusion MRI tractography. Diffusion weighted images from 40 healthy Human Connectome Project (HCP) subjects and our GTS patient were analyzed. The VL posterior nucleus (VLp) and the CM were used as seeds for whole-brain probabilistic tractography. Leads were localized via linear registration of pre-/post-operative imaging and cross-referenced with the DBS Intrinsic Template Atlas. Tractography revealed high streamline probability from the CM and VLp to the superior frontal gyrus, rostral middle frontal gyrus, brainstem, and ventral diencephalon. Given reported variable responses to DBS along the thalamus, we segmented the VLp based on its connectivity profile. Ventral and dorsal subdivisions emerged, with streamline probability patterns differing between the dorsal VLp and CM. The CM, the most reported DBS target for GTS, and the dorsal VLp have different but seemingly complimentary connectivity profiles as evidenced by our patient who, at 1-year post-operatively, had significant therapeutic benefit. Stimulation of both regions may better target reward and motor circuits, resulting in enhanced symptom control for GTS.

Orexin-1 receptor signaling within the lateral hypothalamus, but not bed nucleus of the stria terminalis, mediates context-induced relapse to alcohol seeking.

BACKGROUND: The lateral hypothalamic orexin (hypocretin) system has a well-established role in the motivation for reward. This has particular relevance to substance use disorders since orexin-1 receptors play a critical role in alcohol-seeking behavior, acting at multiple nodes in relapse-associated networks. AIMS: This study aimed to further our understanding of the role of orexin-1 receptor signaling within the lateral hypothalamus and bed nucleus of the stria terminalis, specifically in context-induced relapse to alcohol-seeking following punishment-imposed abstinence. METHODS: We trained inbred male alcohol-preferring rats to self-administer alcohol in one environment or context (Context A) and subsequently punished their alcohol-reinforced lever presses in a different environment (Context B) using contingent foot shock punishment. Finally, we tested rats for relapse-like behavior in either context following systemic, intra-lateral hypothalamus or intra-bed nucleus of the stria terminalis orexin-1 receptor antagonism with SB-334867. RESULTS/OUTCOMES: We found that systemic orexin-1 receptor antagonism significantly reduced alcohol-seeking in both contexts. Intra-lateral hypothalamus orexin-1 receptor antagonism significantly reduced alcohol-seeking in Context A whereas intra-bed nucleus of the stria terminalis orexin-1 receptor antagonism had no effect on alcohol-seeking behavior. CONCLUSIONS/INTERPRETATION: Our results suggest a role for the orexin-1 receptor system in context-induced relapse to alcohol-seeking. Specifically, intra-lateral hypothalamus orexin microcircuits contribute to alcohol-seeking.

Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain.

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.

Visual Response Characteristics in Lateral and Medial Subdivisions of the Rat Pulvinar.

The pulvinar is a higher-order thalamic relay and a central component of the extrageniculate visual pathway, with input from the superior colliculus and visual cortex and output to all of visual cortex. Rodent pulvinar, more commonly called the lateral posterior nucleus (LP), consists of three highly-conserved subdivisions, and offers the advantage of simplicity in its study compared to more subdivided primate pulvinar. Little is known about receptive field properties of LP, let alone whether functional differences exist between different LP subdivisions, making it difficult to understand what visual information is relayed and what kinds of computations the pulvinar might support. Here, we characterized single-cell response properties in two V1 recipient subdivisions of rat pulvinar, the rostromedial (LPrm) and lateral (LPl), and found that a fourth of the cells were selective for orientation, compared to half in V1, and that LP tuning widths were significantly broader. Response latencies were also significantly longer and preferred size more than three times larger on average than in V1; the latter suggesting pulvinar as a source of spatial context to V1. Between subdivisons, LPl cells preferred higher temporal frequencies, whereas LPrm showed a greater degree of direction selectivity and pattern motion detection. Taken together with known differences in connectivity patterns, these results suggest two separate visual feature processing channels in the pulvinar, one in LPl related to higher speed processing which likely derives from superior colliculus input, and the other in LPrm for motion processing derived through input from visual cortex. SIGNIFICANCE STATEMENT: The pulvinar has a perplexing role in visual cognition as no clear link has been found between the functional properties of its neurons and behavioral deficits that arise when it is damaged. The pulvinar, called the lateral posterior nucleus (LP) in rats, is a higher order thalamic relay with input from the superior colliculus and visual cortex and output to all of visual cortex. By characterizing single-cell response properties in anatomically distinct subdivisions we found two separate visual feature processing channels in the pulvinar, one in lateral LP related to higher speed processing which likely derives from superior colliculus input, and the other in rostromedial LP for motion processing derived through input from visual cortex.

Circuitry Underlying Experience-Dependent Plasticity in the Mouse Visual System.

Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders.

Arterial Supply of the Thalamus: A Comprehensive Review.

The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the thalamus can, therefore, result in complex syndromes involving sensation, cognition, executive function, fine motor control, emotion, and arousal, to name a few. Specific territories in the thalamus that are supplied by deep cerebral arteries have been shown to correlate with clinical symptoms. The aim of this review is to enhance our understanding of the arterial anatomy of the thalamus and the complications that can arise from lesions to it by considering the functions of known thalamic nuclei supplied by each vascular territory.

Cross-modal modulation of cell activity by sound in first-order visual thalamic nucleus.

Cross-modal auditory influence on cell activity in the primary visual cortex emerging at short latencies raises the possibility that the first-order visual thalamic nucleus, which is considered dedicated to unimodal visual processing, could contribute to cross-modal sensory processing, as has been indicated in the auditory and somatosensory systems. To test this hypothesis, the effects of sound stimulation on visual cell activity in the dorsal lateral geniculate nucleus were examined in anesthetized rats, using juxta-cellular recording and labeling techniques. Visual responses evoked by light (white LED) were modulated by sound (noise burst) given simultaneously or 50-400 ms after the light, even though sound stimuli alone did not evoke cell activity. Alterations of visual response were observed in 71% of cells (57/80) with regard to response magnitude, latency, and/or burst spiking. Suppression predominated in response magnitude modulation, but de novo responses were also induced by combined stimulation. Sound affected not only onset responses but also late responses. Late responses were modulated by sound given before or after onset responses. Further, visual responses evoked by the second light stimulation of a double flash with a 150-700 ms interval were also modulated by sound given together with the first light stimulation. In morphological analysis of labeled cells projection cells comparable to X-, Y-, and W-like cells and interneurons were all susceptible to auditory influence. These findings suggest that the first-order visual thalamic nucleus incorporates auditory influence into parallel and complex thalamic visual processing for cross-modal modulation of visual attention and perception.

A systematic topographical relationship between mouse lateral posterior thalamic neurons and their visual cortical projection targets.

Higher-order visual thalamus communicates broadly and bi-directionally with primary and extrastriate cortical areas in various mammals. In primates, the pulvinar is a topographically and functionally organized thalamic nucleus that is largely dedicated to visual processing. Still, a more granular connectivity map is needed to understand the role of thalamocortical loops in visually guided behavior. Similarly, the secondary visual thalamic nucleus in mice (the lateral posterior nucleus, LP) has extensive connections with cortex. To resolve the precise connectivity of these circuits, we first mapped mouse visual cortical areas using intrinsic signal optical imaging and then injected fluorescently tagged retrograde tracers (cholera toxin subunit B) into retinotopically-matched locations in various combinations of seven different visual areas. We find that LP neurons representing matched regions in visual space but projecting to different extrastriate areas are found in different topographically organized zones, with few double-labeled cells (~4-6%). In addition, V1 and extrastriate visual areas received input from the ventrolateral part of the laterodorsal nucleus of the thalamus (LDVL). These observations indicate that the thalamus provides topographically organized circuits to each mouse visual area and raise new questions about the contributions from LP and LDVL to cortical activity.

Thalamic nuclei in frontotemporal dementia: Mediodorsal nucleus involvement is universal but pulvinar atrophy is unique to C9orf72.

Thalamic atrophy is a common feature across all forms of FTD but little is known about specific nuclei involvement. We aimed to investigate in vivo atrophy of the thalamic nuclei across the FTD spectrum. A cohort of 402 FTD patients (age: mean(SD) 64.3(8.2) years; disease duration: 4.8(2.8) years) was compared with 104 age-matched controls (age: 62.5(10.4) years), using an automated segmentation of T1-weighted MRIs to extract volumes of 14 thalamic nuclei. Stratification was performed by clinical diagnosis (180 behavioural variant FTD (bvFTD), 85 semantic variant primary progressive aphasia (svPPA), 114 nonfluent variant PPA (nfvPPA), 15 PPA not otherwise specified (PPA-NOS), and 8 with associated motor neurone disease (FTD-MND), genetic diagnosis (27 MAPT, 28 C9orf72, 18 GRN), and pathological confirmation (37 tauopathy, 38 TDP-43opathy, 4 FUSopathy). The mediodorsal nucleus (MD) was the only nucleus affected in all FTD subgroups (16-33% smaller than controls). The laterodorsal nucleus was also particularly affected in genetic cases (28-38%), TDP-43 type A (47%), tau-CBD (44%), and FTD-MND (53%). The pulvinar was affected only in the C9orf72 group (16%). Both the lateral and medial geniculate nuclei were also affected in the genetic cases (10-20%), particularly the LGN in C9orf72 expansion carriers. Use of individual thalamic nuclei volumes provided higher accuracy in discriminating between FTD groups than the whole thalamic volume. The MD is the only structure affected across all FTD groups. Differential involvement of the thalamic nuclei among FTD forms is seen, with a unique pattern of atrophy in the pulvinar in C9orf72 expansion carriers.

Spatial Clustering of Inhibition in Mouse Primary Visual Cortex.

Whether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-2-assisted mapping of excitatory postsynaptic currents (EPSCs) in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP, and cortical feedback is distinct and depends on whether the neurons reside in clusters aligned with patches or interpatches. Paired recordings from PVs and PNs show that unitary inhibitory postsynaptic currents (uIPSCs) are larger in interpatches than in patches. The spatial clustering of inhibition is matched by dense clustering of PV terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks, which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features.

A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice.

The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar-hippocampal connections in the mouse brain using combinations of Recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC) as well as thalamic and cerebellar areas. Whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP, displayed eGFP positive cells in the rhinal cortex and subiculum. To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC and subiculum (S), which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial (FN), interposed (IntP) and lateral (Lat) nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar-hippocampal connection via the laterodorsal and ventrolateral thalamus to RSC, RC and S. These results strengthen the notion of the cerebellum's involvement in cognitive functions such as spatial navigation via a polysynaptic circuitry.

Estradiol Acts in Lateral Thalamic Region to Attenuate Varicella Zoster Virus Associated Affective Pain.

Varicella zoster virus (VZV) results in chicken pox and herpes zoster. Female rats show a higher level of herpes zoster associated pain than males, consistent with human studies. In this study, we addressed the novel hypothesis that sex difference in herpes zoster associated pain is due, in part, to estradiol modulating activity in the thalamus. To test this hypothesis a high and low physiological dose of estradiol was administered to castrated and ovariectomized rats and the affective pain response was measured after injection of VZV into the whisker pad. Thalamic infusion of the estrogen receptor antagonist ICI 182,780 concomitant with a high dose of estradiol addressed the role of estradiol binding to its receptor to effect pain. Phosphorylated extracellular signal-regulated protein kinase (pERK) positive cells were measured in excitatory (glutaminase positive) and inhibitory (glutamate decarboxylase 67 positive) cells of the lateral thalamic region. Our results show that a high dose of estradiol significantly reduced the pain response in both males and females. pERK significantly increased in excitatory cells after treatment with a low dose of estradiol and increased in inhibitory cells after treatment with a high dose of estradiol. Administration of ICI 182,780 significantly increased the pain response, reduced expression of GABA related genes in the thalamic region and significantly reduced the number of inhibitory cells expressing pERK. The results suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons within the thalamus and that this reduction includes an estrogen receptor dependent mechanism.

CREB down-regulation in the laterodorsal thalamic nucleus deteriorates memory consolidation in rats.

The laterodorsal thalamic nucleus (LD) is believed to play roles in learning and memory, especially spatial tasks. However, the molecular mechanism that underlies the cognitive process in the LD remains unclear and needs to be investigated. So far, there is plenty of evidence indicating that plasticity has been in some of the cortical or subcortical regions closely related to the LD, particularly stimulated by external learning tasks. Therefore, the present study aimed to test the hypothesis that similar effect exists in the LD. The transcription factor, cAMP-response element binding protein (CREB), works essentially in brain plasticity by tightly regulating the transcriptional level of memory-related target genes, and the increase of activated CREB (phosphorylated CREB, p-CREB) could facilitate memory consolidation. In this study, the siRNA against CREB was synthesized to down-regulate the CREB mRNA in the LD. After Morris water maze behavioral training, CREB siRNA rats exhibited a memory deficiency, significantly diverging from the control groups. In subsequent detection, the expression of p-CREB of these memory impairment rats attenuated. These results support the hypothesis that CREB-mediated plasticity contributes to memory facilitation and consolidation in the LD.

Selective decrease of cholinergic signaling from pedunculopontine and laterodorsal tegmental nuclei has little impact on cognition but markedly increases susceptibility to stress.

The pedunculopontine tegmental nucleus (PPT) and laterodorsal tegmental nucleus (LDT) are heterogeneous brainstem structures that contain cholinergic, glutamatergic, and GABAergic neurons. PPT/LDT neurons are suggested to modulate both cognitive and noncognitive functions, yet the extent to which acetylcholine (ACh) signaling from the PPT/LDT is necessary for normal behavior remains uncertain. We addressed this issue by using a mouse model in which PPT/LDT cholinergic signaling is highly decreased by selective deletion of the vesicular ACh transporter (VAChT) gene. This approach interferes exclusively with ACh signaling, leaving signaling by other neurotransmitters from PPT/LDT cholinergic neurons intact and sparing other cells. VAChT mutants were examined on different PPT/LDT-associated cognitive domains. Interestingly, VAChT mutants showed no attentional deficits and only minor cognitive flexibility impairments while presenting large deficiencies in both spatial and cued Morris water maze (MWM) tasks. Conversely, working spatial memory determined with the Y-maze and spatial memory measured with the Barnes maze were not affected, suggesting that deficits in MWM were unrelated to spatial memory abnormalities. Supporting this interpretation, VAChT mutants exhibited alterations in anxiety-like behavior and increased corticosterone levels after exposure to the MWM, suggesting altered stress response. Thus, PPT/LDT VAChT-mutant mice present little cognitive impairment per se, yet they exhibit increased susceptibility to stress, which may lead to performance deficits in more stressful conditions.-Janickova, H., Kljakic, O., Rosborough, K., Raulic, S., Matovic, S., Gros, R., Saksida, L. M., Bussey, T. J., Inoue, W., Prado, V. F., Prado, M. A. M. Selective decrease of cholinergic signaling from pedunculopontine and laterodorsal tegmental nuclei has little impact on cognition but markedly increases susceptibility to stress.

Electroacupuncture Treatment Alleviates the Remifentanil-Induced Hyperalgesia by Regulating the Activities of the Ventral Posterior Lateral Nucleus of the Thalamus Neurons in Rats.

Mechanisms underlying remifentanil- (RF-) induced hyperalgesia, a phenomenon that is generally named as opioid-induced hyperalgesia (OIH), still remain elusive. The ventral posterior lateral nucleus (VPL) of the thalamus, a key relay station for the transmission of nociceptive information to the cerebral cortex, is activated by RF infusion. Electroacupuncture (EA) is an effective method for the treatment of pain. This study aimed to explore the role of VPL in the development of OIH and the effect of EA treatment on OIH in rats. RF was administered to rats via the tail vein for OIH induction. Paw withdrawal threshold (PWT) in response to mechanical stimuli and paw withdrawal latency (PWL) to thermal stimulation were tested in rats for the assessment of mechanical allodynia and thermal hyperalgesia, respectively. Spontaneous neuronal activity and local field potential (LFP) in VPL were recorded in freely moving rats using the in vivo multichannel recording technique. EA at 2 Hz frequency (pulse width 0.6 ms, 1-3 mA) was applied to the bilateral acupoints "Zusanli" (ST.36) and "Sanyinjiao" (SP.6) in rats. The results showed that both the PWT and PWL were significantly decreased after RF infusion to rats. Meanwhile, both the spontaneous neuronal firing rate and the theta band oscillation in VPL LFP were increased on day 3 post-RF infusion, indicating that the VPL may promote the development of RF-induced hyperalgesia by regulating the pain-related cortical activity. Moreover, 2 Hz-EA reversed the RF-induced decrease both in PWT and PWL of rats and also abrogated the RF-induced augmentation of the spontaneous neuronal activity and the power spectral density (PSD) of the theta band oscillation in VPL LFP. These results suggested that 2 Hz-EA attenuates the remifentanil-induced hyperalgesia via reducing the excitability of VPL neurons and the low-frequency (theta band) oscillation in VPL LFP.

Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice.

Animals respond to environmental threats, e.g. looming visual stimuli, with innate defensive behaviors such as escape and freezing. The key neural circuits that participate in the generation of such dimorphic defensive behaviors remain unclear. Here we show that the dimorphic behavioral patterns triggered by looming visual stimuli are mediated by parvalbumin-positive (PV+) projection neurons in mouse superior colliculus (SC). Two distinct groups of SC PV+ neurons form divergent pathways to transmit threat-relevant visual signals to neurons in the parabigeminal nucleus (PBGN) and lateral posterior thalamic nucleus (LPTN). Activations of PV+ SC-PBGN and SC-LPTN pathways mimic the dimorphic defensive behaviors. The PBGN and LPTN neurons are co-activated by looming visual stimuli. Bilateral inactivation of either nucleus results in the defensive behavior dominated by the other nucleus. Together, these data suggest that the SC orchestrates dimorphic defensive behaviors through two separate tectofugal pathways that may have interactions.