Early anatomical evidence suggested that the paraventricular nucleus of the thalamus (PVT) regulates arousal, as well as emotional and motivated behaviors. We discuss recent studies using modern ...techniques which now confirm and expand the involvement of the rodent PVT in these functions. Despite the emerging notion that the PVT is implicated in various behavioral processes, a recurrent theme is that activity in this brain region depends on internal state information arriving from the hypothalamus and brainstem, and is influenced by prior experience. We propose that the primary function of the PVT is to detect homeostatic challenges by integrating information about prior experiences, competing needs, and internal state to guide adaptive behavioral responses aimed at restoring homeostasis.
Emerging evidence indicates that the PVT plays a previously overlooked but fundamental role in the control of emotional and motivated behaviors. Heterogeneity within the PVT is thought to underlie diverse functions in behavioral control.We propose that the PVT is an integrative node in which information about prior experiences converges with interoceptive and exteroceptive signals to guide the selection of adaptive behavioral responses that promote homeostasis.We argue that the role of the PVT in homeostatic control is largely influenced by hypothalamic and hindbrain inputs that convey information about internal state.We further argue that, although PVT projections to the nucleus accumbens and the central nucleus of the amygdala may appear to reflect a de facto valenced organization (e.g., reward and fear, respectively), these segregated circuits likely provide a means by which the PVT can influence both goal-directed and Pavlovian-related behavioral responses to homeostatic challenges.The role of the PVT in driving goal-directed behavior may be particularly motivated by negative reinforcement.
A patrimony of technical skills, observations, and knowledge of natural facts, acquired through ages, has been a powerful motor of human progress. Over the last century, scientific progress has ...become impressively fast, thanks to a closer interplay of research and technology. The field of particle physics has witnessed a spectacular evolution, with the construction of huge particle accelerators and colliders, associated with massive experimental apparatus, where engineers and physicists have been closely collaborating. The data from these experiments have brought new discoveries, and new questions as well. Few examples are given of ways in which conceptual advances, technological progress, and experimental ingenuity have conspired towards the solution of fundamental physics problems. New challenges in the future are outlined.
Recent studies indicate that the lateral subdivision of the central amygdala (CeL) is essential for fear learning. Specifically, fear conditioning induces cell-type-specific synaptic plasticity in ...CeL neurons that is required for the storage of fear memories. The CeL also controls fear expression by gating the activity of the medial subdivision of the central amygdala (CeM), the canonical amygdala output to areas that mediate defensive responses. In addition to the connection with CeM, the CeL sends long-range projections to innervate extra-amygdala areas. However, the long-range projection CeL neurons have not been well characterized, and their role in fear regulation is unknown. Here we show in mice that a subset of CeL neurons directly project to the midbrain periaqueductal gray (PAG) and the paraventricular nucleus of the thalamus, two brain areas implicated in defensive behavior. These long-range projection CeL neurons are predominantly somatostatin-positive (SOM(+)) neurons, which can directly inhibit PAG neurons, and some of which innervate both the PAG and paraventricular nucleus of the thalamus. Notably, fear conditioning potentiates excitatory synaptic transmission onto these long-range projection CeL neurons. Thus, our study identifies a subpopulation of SOM(+) CeL neurons that may contribute to fear learning and regulate fear expression independent of CeM.
Unlike the sensory thalamus, studies on the functional organization of the midline and intralaminar nuclei are scarce, and this has hindered the establishment of conceptual models of the function of ...this brain region. We investigated the functional organization of the paraventricular nucleus of the thalamus (PVT), a midline thalamic structure that is increasingly being recognized as a critical node in the control of diverse processes such as arousal, stress, emotional memory and motivation, in mice. We identify two major classes of PVT neurons-termed type I and type II-that differ in terms of gene expression, anatomy and function. In addition, we demonstrate that type II neurons belong to a previously neglected class of PVT neurons that convey arousal-related information to corticothalamic neurons of the infralimbic cortex. Our results uncover the existence of an arousal-modulated thalamo-corticothalamic loop that links the PVT and the ventromedial prefrontal cortex.
For animals to survive, they must reliably predict during foraging which substances are suitable for consumption. Despite extensive study, the neural circuit mechanisms underlying such adaptive ...behavior remain poorly understood. Here, using a tastant (sucrose/quinine)-reinforced "go/no-go" task in male and female mice, we examined the anatomical and functional connectivity of the circuit linking the insular cortex (IC) to the central amygdala (CeA) and the role of this circuit in the establishment of appropriate behavioral responses. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the "no-go" response, and impaired the "go" responses in the go/no-go task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activities in the IC-CeL circuit are critical for establishing taste-reinforced behavioral responses, including avoidance responses to an aversive tastant, and are sufficient to drive learning of anticipatory avoidance. Our findings suggest that the IC-CeL circuit plays an important role in guiding appropriate choices during foraging.
An animal's ability to predict which substances are suitable for consumption and then produce an appropriate action to those substances is critical for survival. Here we found that activity in the circuit that links the insular cortex (IC) to the central amygdala (CeA) is necessary for establishing appropriate behavioral responses to taste-predicting cues. This neural circuit seems to be particularly tuned to avoid an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for generating appropriate behavioral responses during foraging when facing different choices.
Research in fear conditioning has provided a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, our understanding of the retrieval of fear memories ...is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring some clarity and raise awareness about the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points following auditory fear conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus (PVT) for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change with time, and consider the functional strategy of recruiting structures not previously considered as part of the retrieval circuit.
A
bstract
We describe a proposal to add a set of very forward detectors to the CMS experiment for the high-luminosity era of the Large Hadron Collider to search for beyond the standard model ...long-lived particles, such as dark photons, heavy neutral leptons, axion-like particles, and dark Higgs bosons. The proposed subsystem is called
FACET
for
F
orward-
A
perture
C
MS
E
x
T
ension, and will be sensitive to any particles that can penetrate at least 50 m of magnetized iron and decay in an 18 m long, 1 m diameter vacuum pipe. The decay products will be measured in detectors using identical technology to the planned CMS Phase-2 upgrade.
The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked to ...cellular differences, the molecular identity and spatial distribution of PVT cell types remain unclear. To address this gap, here we used single nucleus RNA sequencing (snRNA-seq) and identified five molecularly distinct PVT neuronal subtypes in the mouse brain. Additionally, multiplex fluorescent in situ hybridization of top marker genes revealed that PVT subtypes are organized by a combination of previously unidentified molecular gradients. Lastly, comparing our dataset with a recently published single-cell sequencing atlas of the thalamus yielded novel insight into the PVT's connectivity with the cortex, including unexpected innervation of auditory and visual areas. This comparison also revealed that our data contains a largely non-overlapping transcriptomic map of multiple midline thalamic nuclei. Collectively, our findings uncover previously unknown features of the molecular diversity and anatomical organization of the PVT and provide a valuable resource for future investigations.
Marked deficits in glucose availability, or glucoprivation, elicit organism-wide counter-regulatory responses whose purpose is to restore glucose homeostasis. However, while catecholamine neurons of ...the ventrolateral medulla (VLM
) are thought to orchestrate these responses, the circuit and cellular mechanisms underlying specific counter-regulatory responses are largely unknown. Here, we combined anatomical, imaging, optogenetic and behavioral approaches to interrogate the circuit mechanisms by which VLM
neurons orchestrate glucoprivation-induced food seeking behavior. Using these approaches, we found that VLM
neurons form functional connections with nucleus accumbens (NAc)-projecting neurons of the posterior portion of the paraventricular nucleus of the thalamus (pPVT). Importantly, optogenetic manipulations revealed that while activation of VLM
projections to the pPVT was sufficient to elicit robust feeding behavior in well fed mice, inhibition of VLM
-pPVT communication significantly impaired glucoprivation-induced feeding while leaving other major counterregulatory responses intact. Collectively our findings identify the VLM
-pPVT-NAc pathway as a previously-neglected node selectively controlling glucoprivation-induced food seeking. Moreover, by identifying the ventrolateral medulla as a direct source of metabolic information to the midline thalamus, our results support a growing body of literature on the role of the PVT in homeostatic regulation.
Time measurements with sub-nanosecond time resolution (aiming at values of few picoseconds) are of paramount importance for a wide variety of applications. In the field of particle physics, measuring ...with increasing precision the time taken by a particle to travel between two points (Time-of-Flight, ToF) gives information on the particle' (relativistic) velocity, contributing to identifying the type of particle (Particle Identification Detectors, PID). Among this category of detectors are also Cherenkov counters, based on the emission of light when a charged particle travels in a transparent medium with a velocity exceeding the light velocity in that medium. Here we discuss a special category of ToF counters using the properties of Cherenkov light to determine the passage of the particles through the detectors with unprecedented precision. Results obtained with test beams are described and analysed, demonstrating the excellent timing resolution that can be obtained. Such detectors may be used to provide a 'precision time reference' for calibrating other types of timing detectors. Other applications are, for instance, time-tagging of 'pile-up' events in high-luminosity Large Hadron Collider (LHC), and identification of events with anomalous timing properties (for instance, long-lived particles, LLP).
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