Anteromedial Thalamic Nucleus Research Articles

Possible rodent equivalent of the posterior cingulate cortex (area 23) interconnects with multimodal cortical and subcortical regions.

Posterior cingulate cortex (area 23, A23) in human and monkeys is a critical component of the default mode network and is involved in many diseases such as Alzheimer's disease, autism, depression, attention deficit hyperactivity disorder and schizophrenia. However, A23 has not yet identified in rodents, and this makes modeling related circuits and diseases in rodents very difficult. Using a comparative approach, molecular markers and unique connectional patterns this study has uncovered the location and extent of possible rodent equivalent (A23~) of the primate A23. A23 ~ but not adjoining areas in the rodents displays strong reciprocal connections with anteromedial thalamic nucleus. Rodent A23 ~ reciprocally connects with the medial pulvinar and claustrum as well as with anterior cingulate, granular retrosplenial, medial orbitofrontal, postrhinal, and visual and auditory association cortices. Rodent A23 ~ projects to dorsal striatum, ventral lateral geniculate nucleus, zona incerta, pretectal nucleus, superior colliculus, periaqueductal gray, and brainstem. All these findings support the versatility of A23 in the integration and modulation of multimodal sensory information underlying spatial processing, episodic memory, self-reflection, attention, value assessment and many adaptive behaviors. Additionally, this study also suggests that the rodents could be used to model monkey and human A23 in future structural, functional, pathological, and neuromodulation studies.

Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity

The prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.

Functional connectivity of anterior retrosplenial cortex in object recognition memory

Recognition memory can rely on three components: “what”, “where” and “when”. Recently we demonstrated that the anterior retrosplenial cortex (aRSC), like the perirhinal cortex (PRH) and unlike the hippocampus (HP), is required for consolidation of the “what” component. Here, we aimed at studying which brain structures interact with the aRSC to process object recognition (OR) memory in rats. We studied the interaction of six brain structures that are connected to the aRSC during OR memory processing: PRH, medial prefrontal cortex (mPFC), anteromedial thalamic nuclei (AM), medial entorhinal cortex (MEC), anterior cingulate cortex (ACC) and the dorsal HP (dHP). We previously described the role of the PRH and dHP, so we first studied the participation of the mPFC, AM, MEC and ACC in OR memory consolidation by bilateral microinfusions of the GABAA receptor agonist muscimol. We observed an impairment in OR long-term memory (LTM) when inactivating the mPFC, the AM and the MEC, but not the ACC. Then, we studied the functional connections by unilateral inactivation of the aRSC and each one of the six structures in the same (ipsilateral) or the opposite (contralateral) hemisphere. Our results showed an amnesic LTM effect in rats with ipsilateral inactivations of aRSC-PRH, aRSC-mPFC, aRSC-AM, or aRSC-MEC. On the other hand, we observed memory impairment when aRSC-ACC were inactivated in opposite hemispheres, and no effect when the aRSC-dHP connection was inactivated. Thus, our ipsilateral inactivation findings reveal that the aRSC and, at least one brain region required in OR LTM processing are essential to consolidate OR memory. In conclusion, our results show that several cortico-cortical and cortico-thalamic pathways are important for OR memory consolidation.

Monosynaptic connection from the subiculum to medial mammillary nucleus neurons projecting to the anterior thalamus and Gudden’s ventral tegmental nucleus

As a major hippocampal output structure, the subiculum projects to diverse cortical and subcortical areas, and its projection to the medial mammillary nucleus (MM) has been implicated in memory. Major efferent targets of the MM are the anteroventral and anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus. These projections may play a key role in distributing subicular information. However, it remains unknown whether neurons in the MM that receive monosynaptic input from the subiculum project to these target regions. We addressed this issue with anterograde transsynaptic tracing mediated using adeno-associated virus serotype 1 (AAV1). Injection of AAV1-Cre and a Cre-dependent AAV encoding enhanced yellow fluorescent protein (EYFP) into the rat dorsal subiculum and MM, respectively, labeled the soma of the MM and axons in the anteroventral / anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus with EYFP. The EYFP-positive neurons in the MM were immunoreactive for glutamate and leu-enkephalin and received perisomatic GABAergic inputs. These results revealed monosynaptic projections from the subiculum to MM neurons projecting to the anteroventral / anteromedial thalamic nuclei and Gudden’s ventral tegmental nucleus. This monosynaptic connection may support a fast and robust signal flow through the hippocampal–mammillothalamic and hippocampal–mammillotegmental pathways.

Long-term stimulation of the anteromedial thalamus increases hippocampal neurogenesis and spatial reference memory in adult rats

Deep brain stimulation (DBS) has shown positive clinical results in neurodegenerative diseases. Previous work from our group showed that a single session of DBS to the anteromedial thalamic nucleus (AMN) in awake rats, increased proliferation of stem/progenitor cells in the dentate gyrus (DG) of the hippocampus. We thought to examine the effect of single versus multiple sessions of DBS to the AMN in modulating adult hippocampal neurogenesis. Rats received unilateral single session, multiple sessions or no electrical stimulation (sham) in the right AMN. Rats received 5’-bromo-2’-deoxyuridine (BrdU) injections and were followed over a period of 1 week or 4 weeks. Single session of electrical stimulation induced a 1.9-fold increase in the number of proliferating BrdU positive cells after one week from stimulation and a 1.8-fold increase at four weeks post stimulation, both in the ipsilateral DG. As for multiple sessions of stimulation, they induced a 3- fold increase that extended to the contralateral DG after 4 weeks from stimulation. Spatial reference memory was tested in the Y-maze test by examining novel arm exploration. Both single and multiple sessions of stimulation prompted an increase in novel arm exploration at week 4, while only the multiple sessions of stimulation had this effect starting from week 1. This study demonstrates that sustained activation of the AMN boosts neurogenesis and improves spatial reference memory.

Afferent Projections to Area Prostriata of the Mouse.

Area prostriata plays important roles in fast detection and analysis of peripheral visual information. It remains unclear whether the prostriata directly receives and integrates information from other modalities. To gain insight into this issue, we investigated brain-wide afferent projections to mouse prostriata. We find convergent projections to layer 1 of the prostriata from primary and association visual and auditory cortices; retrosplenial, lateral entorhinal, and anterior cingulate cortices; subiculum; presubiculum; and anterior thalamic nuclei. Innervation of layers 2–3 of the prostriata mainly originates from the presubiculum (including postsubiculum) and anterior midline thalamic region. Layer 5 of the prostriata mainly receives its inputs from medial entorhinal, granular retrosplenial, and medial orbitofrontal cortices and anteromedial thalamic nucleus while layer 6 gets its major inputs from ectorhinal, postrhinal, and agranular retrosplenial cortices. The claustrum, locus coeruleus, and basal forebrain provide relatively diffuse innervation to the prostriata. Moreover, Cre-dependent tracing in cortical areas reveals that the cells of origin of the prostriata inputs are located in layers 2–4 and 5 of the neocortical areas, layers 2 and 5 of the medial entorhinal cortex, and layer 5 of the retrosplenial cortex. These results indicate that the prostriata is a unique region where primary and association visual and auditory inputs directly integrate with many limbic inputs.

Regulation of Cued Fear Expression via Corticotropin-Releasing-Factor Neurons in the Ventral Anteromedial Thalamic Nucleus.

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.

Anteromedial thalamic nucleus to anterior cingulate cortex inputs modulate histaminergic itch sensation

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.

Revealing a Cortical Circuit Responsive to Predatory Threats and Mediating Contextual Fear Memory

The ventral part of the anteromedial thalamic nucleus (AMv) receives substantial inputs from hypothalamic sites that are highly responsive to a live predator or its odor trace and represents an important thalamic hub for conveying predatory threat information to the cerebral cortex. In the present study, we begin by examining the cortico-amygdalar-hippocampal projections of the main AMv cortical targets, namely, the caudal prelimbic, rostral anterior cingulate, and medial visual areas, as well as the rostral part of the ventral retrosplenial area, one of the main targets of the anterior cingulate area. We observed that these areas form a clear cortical network. Next, we revealed that in animals exposed to a live cat, all of the elements of this circuit presented a differential increase in Fos, supporting the idea of a predator threat-responsive cortical network. Finally, we showed that bilateral cytotoxic lesions in each element of this cortical network did not change innate fear responses but drastically reduced contextual conditioning to the predator-associated environment. Overall, the present findings suggest that predator threat has an extensive representation in the cerebral cortex and revealed a cortical network that is responsive to predatory threats and exerts a critical role in processing fear memory.

Influence of the anteromedial thalamus on social defeat-associated contextual fear memory

The ventral part of the anteromedial thalamic nucleus (AMv) is heavily targeted by the dorsal premammillary nucleus (PMd), which is the main hypothalamic site that is responsive to both predator and conspecific aggressor threats. This PMd-AMv pathway is likely involved in modulating memory processing, and previous findings from our group have shown that cytotoxic lesions or pharmacological inactivation of the AMv drastically reduced contextual fear responses to predator-associated environments. In the present study, we investigated the role of the AMv in both unconditioned (i.e., fear responses during social defeat) and contextual fear responses (i.e., during exposure to a social defeat-associated context). We addressed this question by placing N-methyl-d-aspartate (NMDA) lesions in the AMv and testing unconditioned fear responses during social defeat and contextual fear responses during exposure to a social defeat-associated context. Accordingly, bilateral AMv lesions did not change unconditioned responses, but decreased contextual conditioning related to social defeat. Notably, our bilateral AMv lesions also included, to a certain degree, the nucleus reuniens (RE), but single RE lesions did not affect innate or contextual fear responses. Overall, our results support the idea that the AMv works as a critical hub, receiving massive inputs from a hypothalamic site that is largely responsive to social threats and transferring social threat information to circuits involved in the processing of contextual fear memories.

Asymmetric cross-hemispheric connections link the rat anterior thalamic nuclei with the cortex and hippocampal formation

Dense reciprocal connections link the rat anterior thalamic nuclei with the prelimbic, anterior cingulate and retrosplenial cortices, as well as with the subiculum and postsubiculum. The present study compared the ipsilateral thalamic-cortical connections with the corresponding crossed, contralateral connections between these same sets of regions. All efferents from the anteromedial thalamic nucleus to the cortex, as well as those to the subiculum, remained ipsilateral. In contrast, all of these target sites provided reciprocal, bilateral projections to the anteromedial nucleus. While the anteroventral thalamic nucleus often shared this same asymmetric pattern of cortical connections, it received relatively fewer crossed inputs than the anteromedial nucleus. This difference was most marked for the anterior cingulate projections, as those to the anteroventral nucleus remained almost entirely ipsilateral. Unlike the anteromedial nucleus, the anteroventral nucleus also appeared to provide a restricted, crossed projection to the contralateral retrosplenial cortex. Meanwhile, the closely related laterodorsal thalamic nucleus had almost exclusively ipsilateral efferent and afferent cortical connections. Likewise, within the hippocampus, the postsubiculum seemingly had only ipsilateral efferent and afferent connections with the anterior thalamic and laterodorsal nuclei. While the bilateral cortical projections to the anterior thalamic nuclei originated predominantly from layer VI, the accompanying sparse projections from layer V largely gave rise to ipsilateral thalamic inputs. In testing a potentially unifying principle of anterior thalamic – cortical interactions, a slightly more individual pattern emerged that reinforces other evidence of functional differences within the anterior thalamic and also helps to explain the consequences of unilateral interventions involving these nuclei.

EP 31. Deep brain stimulation-induced neurogenesis is gender-independent

Background Deep brain stimulation (DBS) provides substantial clinical benefits for a variety of movement disorders and lately emerged as a potential treatment for cognitive and mood disorders. Regulation of adult hippocampal neurogenesis may play a chief role in mediating DBS effects. Nevertheless, there exist significant sex differences in the regulation of neurogenesis influenced mainly by gonadal hormone exposure. Objective To investigate the hippocampal neurogenic differences between male and female awake and unrestrained rats in response to unilateral anteromedial thalamic nucleus (AMN) stimulation. Methods Four groups of adult Sprague-Dawley male and female rats received unilateral stimulation ( n = 6 each) or sham surgery of electrode implantation with no current delivery ( n = 4 each) in the right AMN; A naive group of males and females ( n = 4 each) was also included. Rats received 4 injections (50 mg/Kg/injection) of 5′-bromo-2′-deoxyuridine (BrdU) 3 days post-surgery and were euthanized 24h later. The fractionator method was used together with confocal immunofluorescent analysis to probe for BrdU-, GFAP- and NeuN-positive cells in the dentate gyrus (DG). Results Focal neurogenesis was induced in the ipsilateral DG after AMN stimulation. Stimulation-induced effects were gender-independent and translated into a 76% increase in proliferation of neural stem/progenitor cells. Conclusions Despite the difference in basal neurogenic level between male and female rats, the current study demonstrates that DBS elicits gender-independent neurogenic effects that might have implications in the treatment of cognitive and behavioral disorders irrespective of sex of patients.

A role for the anteromedial thalamic nucleus in the acquisition of contextual fear memory to predatory threats.

Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.

Complementary subicular pathways to the anterior thalamic nuclei and mammillary bodies in the rat and macaque monkey brain.

The origins of the hippocampal (subicular) projections to the anterior thalamic nuclei and mammillary bodies were compared in rats and macaque monkeys using retrograde tracers. These projections form core components of the Papez circuit, which is vital for normal memory. The study revealed a complex pattern of subicular efferents, consistent with the presence of different, parallel information streams, whose segregation appears more marked in the rat brain. In both species, the cells projecting to the mammillary bodies and anterior thalamic nuclei showed laminar separation but also differed along other hippocampal axes. In the rat, these diencephalic inputs showed complementary topographies in the proximal–distal (columnar) plane, consistent with differential involvement in object‐based (proximal subiculum) and context‐based (distal subiculum) information. The medial mammillary inputs, which arose along the anterior–posterior extent of the rat subiculum, favoured the central subiculum (septal hippocampus) and the more proximal subiculum (temporal hippocampus). In contrast, anterior thalamic inputs were largely confined to the dorsal (i.e. septal and intermediate) subiculum, where projections to the anteromedial nucleus favoured the proximal subiculum while those to the anteroventral nucleus predominantly arose in the distal subiculum. In the macaque, the corresponding diencephalic inputs were again distinguished by anterior–posterior topographies, as subicular inputs to the medial mammillary bodies predominantly arose from the posterior hippocampus while subicular inputs to the anteromedial thalamic nucleus predominantly arose from the anterior hippocampus. Unlike the rat, there was no clear evidence of proximal–distal separation as all of these medial diencephalic projections preferentially arose from the more distal subiculum.

Thalamic Stimulation in Awake Rats Induces Neurogenesis in the Hippocampal Formation.

Deep brain stimulation (DBS) provides clinical benefits for a variety of movement disorders and lately emerged as a potential treatment for cognitive and mood disorders. Modulation of adult hippocampal neurogenesis may play a role in mediating its effects. To investigate the effects of unilateral anteromedial thalamic nucleus (AMN) stimulation on adult hippocampal neurogenesis in awake and unrestrained rats. Four groups of adult Sprague-Dawley male and female rats received unilateral stimulation (n = 6 each) or sham surgery (n = 4 each) in the right AMN; another group of males (n = 4) was stimulated in the right ventral posterolateral thalamic nucleus (VPL). A naive group of males and females (n = 4 each) was also included. Rats received 4 injections (50 mg/kg/injection) of 5'-bromo-2'-deoxyuridine (BrdU) 3 days post-surgery and were euthanized 24 h later. The fractionator method was used together with confocal microscopy to count BrdU, GFAP and NeuN positive cells in the dentate gyrus (DG) and hilar zone of the hippocampus. Focal neurogenesis was induced in the ipsilateral DG after AMN but not VPL stimulation. Stimulation-induced effects were sex-independent and translated into a 76% increase in proliferation of neural stem/progenitor cells. Increased neurogenesis was most prominent at the caudal region of the DG, while no effect was detected in the hilar and the subventricular zones. The exclusive hippocampal neurogenic response to AMN stimulation suggests an involvement of the Papez circuitry in mediating DBS effects and in the treatment of cognitive and behavioral disorders.

Fornical and nonfornical projections from the rat hippocampal formation to the anterior thalamic nuclei.

ABSTRACTThe hippocampal formation and anterior thalamic nuclei form part of an interconnected network thought to support memory. A central pathway in this mnemonic network comprises the direct projections from the hippocampal formation to the anterior thalamic nuclei, projections that, in the primate brain, originate in the subicular cortices to reach the anterior thalamic nuclei by way of the fornix. In the rat brain, additional pathways involving the internal capsule have been described, linking the dorsal subiculum to the anteromedial thalamic nucleus, as well as the postsubiculum to the anterodorsal thalamic nucleus. Confirming such pathways is essential in order to appreciate how information is transferred from the hippocampal formation to the anterior thalamus and how it may be disrupted by fornix pathology. Accordingly, in the present study, pathway tracers were injected into the anterior thalamic nuclei and the dorsal subiculum of rats with fornix lesions. Contrary to previous descriptions, projections from the subiculum to the anteromedial thalamic nucleus overwhelmingly relied on the fornix. Dorsal subiculum projections to the majority of the anteroventral nucleus also predominantly relied on the fornix, although postsubicular inputs to the lateral dorsal part of the anteroventral nucleus, as well as to the anterodorsal and laterodorsal thalamic nuclei, largely involved a nonfornical pathway, via the internal capsule. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.

A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata

Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double-labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double-labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III-IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double-labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals.

Colocalization pattern of calbindin and cocaine- and amphetamine-regulated transcript in the mammillary body–anterior thalamic nuclei axis of the guinea pig

The study describes for the first time the colocalization pattern of calbindin (CB) and cocaine- and amphetamine-regulated transcript (CART) in the mammillary body (MB) and anterior thalamic nuclei (ATN) – structures connected in a topographically organized manner by the mammillothalamic tract (mtt). Immunohistochemical study was performed on fetal (E40, E50, E60), newborn (P0) and postnatal (P20, P80) brains of the guinea pig, but the coexistence pattern of the substances was invariable throughout the examined developmental stages. CB and CART colocalized in the perikarya of the lateral part of the medial mammillary nucleus (MMl), whereas in its medial part (MMm) only CB was detected. In the mtt, which originates from the MB, both the substances were present and colocalized in single fibers. Next, fibers from the mtt spread toward the ATN in a particular way: fibers containing CB ran to both the anteromedial thalamic nucleus (AM) and anteroventral thalamic nucleus (AV), while fibers containing CART ran mostly to the latter one. In the ventral part of AV, CB and CART colocalized vastly in the neuropil. The lateral mammillary nucleus and anterodorsal thalamic nucleus were virtually devoid of CB- and CART-positive structures. Based on the known connections between the MB and ATN, we conclude that the studied substances may cooperate in the MMl–AV part of the axis and CB plays a significant role in the MMm–AM part.

Segregation of parallel inputs to the anteromedial and anteroventral thalamic nuclei of the rat

Many brain structures project to both the anteroventral thalamic nucleus and the anteromedial thalamic nucleus. In the present study, pairs of different tracers were placed into these two thalamic sites in the same rats to determine the extent to which these nuclei receive segregated inputs. Only inputs from the laterodorsal tegmental nucleus, the principal extrinsic cholinergic source for these thalamic nuclei, showed a marked degree of collateralization, with approximately 13% of all cells labeled in this tegmental area projecting to both nuclei. Elsewhere, double-labeled cells were very scarce, making up ∼1% of all labeled cells. Three general patterns of anterior thalamic innervation were detected in these other areas. In some sites, e.g., prelimbic cortex, anterior cingulate cortex, and secondary motor area, cells projecting to the anteromedial and anteroventral thalamic nuclei were closely intermingled, with often only subtle distribution differences. These same projections were also often intermingled with inputs to the mediodorsal thalamic nucleus, but again there was little or no collateralization. In other sites, e.g., the subiculum and retrosplenial cortex, there was often less overlap of cells projecting to the two anterior thalamic nuclei. A third pattern related to the dense inputs from the medial mammillary nucleus, where well-defined topographies ensured little intermingling of the neurons that innervate the two thalamic nuclei. The finding that a very small minority of cortical and limbic inputs bifurcates to innervate both anterior thalamic nuclei highlights the potential for parallel information streams to control their functions, despite arising from common regions.

Neuroanatomical distribution of μ-opioid receptor mRNA and binding in monogamous prairie voles (Microtus ochrogaster) and non-monogamous meadow voles (Microtus pennsylvanicus)

The opiate system has long been implicated in the rewarding properties of social interactions. In particular, the μ-opioid receptor (MOR) mediates multiple forms of social attachment, including the attachment of offspring to the mother and social bonding between mates. We have previously shown that MOR in the caudate-putamen is involved in partner preference formation in monogamous prairie voles. Here, using in situ hybridization and receptor autoradiography, we mapped in detail the distribution of MOR mRNA and ligand binding in monogamous prairie vole brains and compared MOR binding density with that of promiscuous meadow vole brains. Comparison of MOR binding in these closely related species with distinctly different social behavior revealed that while the distribution of MOR is similar, prairie voles have significantly higher densities of MOR than meadow voles in a majority of regions in the forebrain, including the caudate-putamen, nucleus accumbens shell, lateral septum and several thalamic nuclei, including the anteroventral and anteromedial thalamic nuclei. These differences in MOR expression between prairie and meadow voles could potentially contribute to species differences in behavior, including social attachment.