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The ventral part of the anteromedial thalamic nucleus (AMv) is in a position to convey information to the cortico-hippocampal-amygdalar circuit involved in the processing of fear memory. Corticotropin-releasing-factor (CRF) neurons are closely associated with the regulation of stress and fear. However, few studies have focused on the role of thalamic CRF neurons in fear memory. In the present study, using a conditioned fear paradigm in CRF transgenic mice, we found that the c-Fos protein in the AMv CRF neurons was significantly increased after cued fear expression. Chemogenetic activation of AMv CRF neurons enhanced cued fear expression, whereas inhibition had the opposite effect on the cued fear response. Moreover, chemogenetic manipulation of AMv CRF neurons did not affect fear acquisition or contextual fear expression. In addition, anterograde tracing of projections revealed that AMv CRF neurons project to wide areas of the cerebral cortex and the limbic system. These results uncover a critical role of AMv CRF neurons in the regulation of conditioned fear memory. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00592-6) contains supplementary material, which is available to authorized users.

Itch is an unpleasant feeling that triggers scratching behavior. Much progress has been made in identifying the mechanism of itch at the peripheral and spinal levels, however, itch circuits in the brain remain largely unexplored. We previously found that anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) inputs modulated histamine-induced itch sensation, but how itch information was transmitted to ACC remained unclear. Here, we demonstrated that the anteromedial thalamic nucleus (AM) was activated during histaminergic itch, and there existed reciprocal neuronal projections between AM and ACC. Disconnection between AM and ACC resulted in a significant reduction of histaminergic, but not nonhistaminergic, itch-related scratching behavior. Optogenetic activation of AM-ACC, but not ACC-AM, projections evoked histaminergic itch sensation. Thus, our studies firstly reveal that AM is critical for histaminergic itch sensation and AM-ACC projections modulate histaminergic itch-induced scratching behavior.

Damage involving the anterior thalamic and adjacent rostral thalamic nuclei may result in a severe anterograde amnesia, similar to the amnesia resulting from damage to the hippocampal formation. Little is known, however, about the information represented in these nuclei. To redress this deficit, we recorded units in three rostral thalamic nuclei in freely-moving rats [the parataenial nucleus (PT), the anteromedial nucleus (AM) and nucleus reuniens NRe]. We found units in these nuclei possessing previously unsuspected spatial properties. The various cell types show clear similarities to place cells, head direction cells, and perimeter/border cells described in hippocampal and parahippocampal regions. Based on their connectivity, it had been predicted that the anterior thalamic nuclei process information with high spatial and temporal resolution while the midline nuclei have more diffuse roles in attention and arousal. Our current findings strongly support the first prediction but directly challenge or substantially moderate the second prediction. The rostral thalamic spatial cells described here may reflect direct hippocampal/parahippocampal inputs, a striking finding of itself, given the relative lack of place cells in other sites receiving direct hippocampal formation inputs. Alternatively, they may provide elemental thalamic spatial inputs to assist hippocampal spatial computations. Finally, they could represent a parallel spatial system in the brain.

Deep brain stimulation (DBS) is a potentially potent means for disrupting the aberrant rhythms that arise during a seizure. However, current DBS strategies typically employed are formulated a priori and do not reflect dynamics within the brain during ictogenesis which may severely limit stimulation efficacy. This study investigated how DBS could be improved using endogenous dynamics to inform stimulation protocols. Multi-site brain dynamics within the circuit of Papez was calculated in a chronic rat limbic epilepsy model. Stimulation/recording electrodes were placed in the CA3 region of both hippocampi and in the anteromedial nucleus of the thalamus. Deconvolution of signals using empirical mode decomposition and coherence analysis were used to identify key dynamics as seizures progressed. Synchronization of field potentials across sites occurred as both spontaneous and evoked seizures naturally terminated. The location and frequency of synchrony varied between subjects suggesting that endogenous rhythms during natural seizure termination may vary in humans as well. DBS efficacy was significantly more effective at stopping seizures when the frequency of multisite synchronized stimulation reflected endogenous synchrony dynamics observed in each subject. Thus, tailoring DBS protocols to individual endogenous rhythms that may represent how brains naturally resolve epileptic seizures could play a critical role in improving overall efficacy of this potentially important therapy.

This study describes for the first time the distribution of the calcium-binding protein calretinin (CR) in the anterior thalamic nuclei (ATN) of the guinea pig during development. Brains from animals ranging from 40th embryonic day (E40) to 80th postnatal day (P80) were used in the study. No CR-immunoreactive (CR-ir) perikarya were present among the ATN at E40, but thick bundles of fibers containing CR were crossing the anteromedial nucleus (AM). The first CR-ir neurons appeared at E50 in the lateral part of the AM. At E60, the bundles of fibers disappeared and the whole area of AM displayed closely packed CR-ir perikarya. At this stage, CR also appeared in neurons of the anteroventral nucleus (AV), particularly in its lateral part and along its dorsal border. Moreover, from E50 short and thin bundles of fibers were observed in the medial part of the AV. The ATN of newborns (P0) already showed an adult-like CR distribution pattern - perikarya in the AM and AV were distributed more homogenously and their number was slightly decreased in comparison to E60. The anterodorsal nucleus (AD) was devoid of CR-ir neurons in all studied stages. In conclusion, our results demonstrate that calretinin appears for the first time in neurons of various anterior thalamic nuclei of the guinea pig between 40th and 60th day of prenatal development.

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd’s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues.

Spontaneous spike activity in three anterior (limbic) neurons of the thalamic nucleus was studied by means of extracellular recording during chronic experiments on anesthetized rabbits. Neurons of the anteroventral nucleus showed high mean rate (24.8±5.8 spikes/sec) and varying structure of spike discharges ("inactivating" bursts of discharges, modulations in delta- and theta-rhythms, and bursts of discharges with a spindle rhythm of 12–14 Hz). "Inactivating" bursts of discharges alternating with single discharges predominated in the activity of neurons of the anteromedial nucleus (mean rate 10.0±1.4 spikes/sec). Activity of the anterodorsal nucleus could be clearly distinguished by the predominance of high-frequency groups of spikes (mean group frequency 67±5 spikes/sec) with prolonged intervals between groups.

Thalamic projections to the medial cortex (cingulate cortex and presubiculum) were studied by the use of anterograde degeneration methods. Observations made in rats with various lesions of the anterio

Thalamic projections to the medial cortex (cingulate cortex and presubiculum) were studied by the use of anterograde degeneration methods. Observations made in rats with various lesions of the anterio

Thalamic afferents to the limbic cortex in the cat were studied with the method of retrograde axonal transport of horseradish peroxidase. The anterior limbic region receives fibers largely from the anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei. There appears to be a dorsoventral organization of cortical projections of the anteromedial nucleus to the anterior limbic region. The cingular area has its main input from the anteroventral and anteromedial nuclei. The lower bank and fundus of the splenial sulcus receive fibers from the anteroventral nucleus, particularly its parvocellular part. The retrosplenial area receives projections from the naterodorsal, anteroventral and anteromedial nuclei. The agranular retrosplenial area (area 30) recieves hardly any fibers from the anterior thalamic nuclei. The postsubicular and presubicular areas receive cortical afferents from the anterodorsal, anteroventral (both magnocellular and parvocellular parts) and anteromedial nuclei. In addition, the limbic cortex receives many fibers from the dorsal lateral, medial pulvinar and lateral pulvinar nuclei, and few fibers from the intralaminar and midline nuclei.