Anteromedial Nucleus Research Articles

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

Collateral rostral thalamic projections to prelimbic, infralimbic, anterior cingulate and retrosplenial cortices in the rat brain.

As the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral thalamic nuclei that terminate across prefrontal (including anterior cingulate) and retrosplenial areas in the rat brain. Two retrograde tracers, fast blue and cholera toxin B, were injected in pairs to different combinations of cortical areas. The research focused on the individual anterior thalamic nuclei, including the interanteromedial nucleus, nucleus reuniens and the laterodorsal nucleus. Of the principal anterior thalamic nuclei, only the anteromedial nucleus contained neurons reaching both the anterior cingulate cortex and adjacent cortical areas (prefrontal or retrosplenial), though the numbers were modest. For these same cortical pairings (medial prefrontal/anterior cingulate and anterior cingulate/retrosplenial), the interanteromedial nucleus and nucleus reuniens contained slightly higher proportions of bifurcating neurons (up to 11% of labelled cells). A contrasting picture was seen for collaterals reaching different areas within retrosplenial cortex. Here, the anterodorsal nucleus, typically provided the greatest proportion of bifurcating neurons (up to 15% of labelled cells). While individual neurons that terminate in different retrosplenial areas were also found in the other thalamic nuclei, they were infrequent. Consequently, these thalamo-cortical projections predominantly arise from separate populations of neurons with discrete cortical termination zones, consistent with the transmission of segregated information and influence. Overall, two contrasting medial-lateral patterns of collateral projections emerged, with more midline nuclei, for example, nucleus reuniens and the interoanteromedial nucleus innervating prefrontal areas, while more dorsal and lateral anterior thalamic collaterals innervated retrosplenial cortex.

Postnatal development of thalamic reticular nucleus projections to the anterior thalamic nuclei in rats.

The thalamic reticular nucleus (TRN) projects inhibitory signals to the thalamus, thereby controlling thalamocortical connections. Few studies have examined the development of TRN projections to the anterior thalamic nuclei with regard to axon course and the axon terminal distributions. In the present study, we used parvalbumin (PV) immunostaining to investigate inhibitory projections from the TRN to the thalamus in postnatal (P) 2- to 5-week-old rats (P14–35). The distribution of PV-positive (+) nerve fibers and nerve terminals markedly differed among the anterior thalamic nuclei at P14. Small, beaded nerve terminals were more distributed throughout the anterodorsal nucleus (AD) than in the anteroventral nucleus (AV) and anteromedial nucleus (AM). PV+ fibers traveling from the TRN to the AD were observed in the AV and AM. Nodular nerve terminals, spindle or en passant terminals, were identified on the axons passing through the AV and AM. At P21, axon bundles traveling without nodular terminals were observed, and nerve terminals were distributed throughout the AV and AM similar to the AD. At P28 and P35, the nerve terminals were evenly distributed throughout each nucleus. In addition, DiI tracer injections into the retrosplenial cortex revealed retrogradely-labeled projection neurons in the 3 nuclei at P14. At P14, the AD received abundant projections from the TRN and then projected to the retrosplenial cortex. The AV and AM seem to receive projections with distinct nodular nerve terminals from the TRN and project to the retrosplenial cortex. The projections from TRN to the AV and AM with nodular nerve terminals at P14 are probably developmental-period specific. In comparison, the TRN projections to the AD at P14 might be related to the development of spatial navigation as part of the head orientation system.

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.

A direct comparison of ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: clinical and imaging evidence for dissociable Effects

A direct comparison of ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: clinical and imaging evidence for dissociable Effects

Identification method and electrophysiological evaluation of cerebellum-projecting anteromedial nucleus neurons by retrograded fluorescence probe

Objective To explore sufficient ways to identify the anteromedial nucleus (MVNs) neurons that project to the cerebellum and evaluate their activity. Methods Retrograde fluorescence probe injection techniques were in vivo applicated to MVNs neurons that project to the cerebellum, neutral red staining was used to determine cell survival time, electrophysiological characteristics by whole cell patch clamp technique were recorded between retrograde labeled anteromedial nucleus neurons projecting to the cerebellum (CPMVNs) and unlabeled MVNs. Results Typical electrophysiological characteristics of retrograde labeled CPMVNs, including spontaneous firing frequency, membrane potential, excitatory presynaptic glutamate afferent and inhibitory postsynaptic gamma aminobutyric acid (GABA) ergic afferent showed no statistical significance, compared with unlabeled MVNs. The amplitudes of monosynaptically evoked excitatory postsynaptic currents (eEPSCs) were respectively (267.100±7.563) pA (n=18), (266.900±6.730) pA (n=25), P=0.962. The current amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) were respectively(19.320±1.768)pA and (2.936±0.512) Hz (n=21), (18.360±1.700) pA and (2.871±0.454) Hz (n=27), with P values were 0.207, 0.755 separately, which showed no statistical significance. Conclusion Vivo application of retrograde fluorescence probe injection techniques helps to identify good CPMVNs, which are specific subjectsfor further study on synaptic transmission mechanism of vestibular-cerebellum pathway. Key words: Medial vestibular nucleus; Electrophysiology; Netrograde label; Brain slice; Synaptic transmission

Commentary: 2016 Epilepsia Basic Science Prize.

Commentary: 2016 Epilepsia Basic Science Prize.

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.

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.

Should stimulation parameters be individualized to stop seizures: Evidence in support of this approach.

Deep-brain electrical stimulation (DBS) is a treatment modality being explored for many neurologic diseases and is a potentially potent means of disrupting the aberrant rhythms that arise during the epileptic seizures that afflict >1% of the population. However, current DBS protocols typically employed are formulated a priori and do not reflect the electrophysiologic dynamics within the brain as seizures arise, which may underlie their limited efficacy. This study investigates how the efficacy of DBS could be improved using endogenous dynamics to inform stimulation protocols. Multisite brain dynamics within the circuit of Papez were calculated in a chronic rat limbic epilepsy model induced via lithium chloride/pilocarpine intraperitoneal injections. Stimulation/recording electrodes were placed in the CA3 region of the left and right hippocampi and the anteromedial nucleus of the left thalamus. Deconvolution of local field potentials using empirical mode decomposition (EMD) and phase synchrony analysis revealed multisite coherence as seizures approached natural termination that could not be detected with Fourier analysis. Multisite stimulation used charge-neutral biphasic square waves at frequencies observed during natural termination. Synchronization of electrical activity across sites occurred as both spontaneous and evoked seizures naturally terminated. Furthermore, the location and frequency of the synchrony varied between subjects but was stable in time within each animal. DBS protocols were significantly more effective at rapidly stopping seizures when the frequency and location of multisite stimulation reflected the endogenous synchrony dynamics observed in each subject as seizures naturally terminated. These results strongly support the approach of tailoring DBS protocols to individual endogenous rhythms that may represent how brains naturally resolve epileptic seizures. This approach may significantly improve the overall efficacy of this potentially important therapy.

Evidence for spatially-responsive neurons in the rostral thalamus.

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.

Central pupillary light reflex circuits in the cat: I. The olivary pretectal nucleus.

The central pathways subserving the feline pupillary light reflex were examined by defining retinal input to the olivary pretectal nucleus (OPt), the midbrain projections of this nucleus, and the premotor neurons within it. Unilateral intravitreal wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections revealed differences in the pattern of retinal OPt termination on the two sides. Injections of WGA-HRP into OPt labeled terminals bilaterally in the anteromedian nucleus, and to a lesser extent in the supraoculomotor area, centrally projecting Edinger-Westphal nucleus, and nucleus of the posterior commissure. Labeled terminals, as well as retrogradely labeled multipolar cells, were present in the contralateral OPt, indicating a commissural pathway. Injections of WGA-HRP into the anteromedian nucleus labeled fusiform premotor neurons within the OPt, as well as multipolar cells in the nucleus of the posterior commissure. Connections between retinal terminals and the pretectal premotor neurons were characterized by combining vitreous chamber and anteromedian nucleus injections of WGA-HRP in the same animal. Fusiform-shaped, retrogradely labeled cells fell within the anterogradely labeled retinal terminal field in the OPt. Ultrastructural analysis revealed labeled retinal terminals containing clear spherical vesicles. They contacted labeled pretectal premotor neurons via asymmetric synaptic densities. These results provide an anatomical substrate for the pupillary light reflex in the cat. Pretectal premotor neurons receive direct retinal input via synapses suggestive of an excitatory drive, and project directly to nuclei containing preganglionic motoneurons. These projections are concentrated in the anteromedian nucleus, indicating its involvement in the pupillary light reflex.

Central pupillary light reflex circuits in the cat: II. Morphology, ultrastructure, and inputs of preganglionic motoneurons.

Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal, and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure, and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting that their activity may be modified by a variety of inputs. Furthermore, there were differences in the synaptic populations contacting the rostral vs. caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population, indicating that these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural, and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, whereas more caudal elements control the lens.

Embryonic and postnatal development of calcium-binding proteins immunoreactivity in the anterior thalamus of the guinea pig

Our recent studies have shown that the distribution of calretinin (CR) in the anterior thalamic nuclei (ATN) changes significantly during the development of the guinea pig. The present study was designed to reveal the distribution pattern of calcium-binding proteins, i.e. calbindin (CB) and parvalbumin (PV), as well as the colocalization pattern of all three proteins, including CR, in the ATN of guinea pigs ranging from the 40th embryonic day (E40) to the 80th postnatal day (P80). According to these patterns, CB appears exclusively in the perikarya of the anteromedial nucleus (AM) not before P20 and always colocalizes with CR. Moreover, CB and CR colocalize in fibers of thin bundles traversing the anteroventral nucleus (AV) since E50. The ATN also display CB-positive neuropil in all studied stages, especially a strong one in the ventral part of the AV. PV was not observed in the perikarya of the ATN in all the stages, but was abundantly present in the neuropil of the anterodorsal nucleus (AD). No colocalizations exist between PV and the rest of the studied proteins. In conclusion, our study reveals that the distribution of the studied proteins differs greatly. Nevertheless, the postnatal coexistence of CB and CR in the AM perikarya may indicate the cooperation of both of the proteins in some functions of the nucleus. Parvalbumin is limited mostly to the neuropil of the AD, suggesting different functions in comparison to CB and CR.

Rapid onset of a kainate-induced mirror focus in rat hippocampus is mediated by contralateral AMPA receptors

The development of an epileptic "mirror" focus in an area of the brain contralateral to the primary epileptic focus typically evolves over days in the experimental setting after status epilepticus or electrical kindling of the primary focal region. In contrast, we observed the rapid development of an apparent mirror focus in the contralateral hippocampus following microinjection of kainic acid (KA) in the ipsilateral hippocampus in rats. Using multisite intracranial recordings, local field potentials were recorded in anesthetized adult male rats using electrodes implanted in the CA3 region of both hippocampi and in the anteromedial nucleus of the thalamus. Epileptogenesis was induced by microinjection of KA in the ipsilateral CA3 region. Development of seizures was followed under three experimental perturbations to the contralateral hippocampus: (A) no treatment, (B) pre-treatment with microinjection of the AMPA/Kainate receptor antagonist CNQX, and (C) pre-treatment with microinjection of the selective kainate receptor antagonist UBP 301. Both control and UBP 301 groups had seizures preferentially originate in the contralateral hippocampus appearing within ten minutes of KA injection. In contrast, the CNQX group had seizures preferentially originate in the ipsilateral hippocampus. By tracking the order of seizure onset, the probability that a hippocampal seizure would propagate across commissural fibers prior to any thalamic seizure activity was significantly reduced in the CNQX group compared to control and UBP groups suggesting that the AMPA receptor mediated component responsible for mirror focus development was also necessary for the spread of ictal activity via the commissural fibers. Understanding how a complex circuit in the brain develops may be critical to uncovering ways of either disrupting its development or treating its effects. The rapid appearance of a contralateral mirror focus via AMPA receptors in a limbic epilepsy model might be the mechanism by which a putative long-term mirror focus is established in vivo and may also underlie how secondary generalization progresses in some cases.

Developmental changes of calretinin immunoreactivity in the anterior thalamic nuclei of the guinea pig

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.

Thalamocortical projections of the anterodorsal thalamic nucleus in the rabbit

The anterior thalamic nuclei consist of the anterodorsal (AD), anteroventral, and anteromedial nuclei, each of which are highly differentiated and may contribute to different aspects of various cognitive and memory functions. In particular, the AD is unique in that it is implicated in learning at the earliest stage of discriminative avoidance conditioning in the rabbit. To better understand the functional roles played by the AD in memory and learning processes, we analyzed the organization of thalamocortical projections of the AD in the rabbit, using the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin subunit B. The data show that the AD provides strong projections to layers I and IV of area 30 and to layers I, III, IV, and VI of area 29 in the retrosplenial cortex, and to layers I and III-VI of the presubiculum. The projections to the retrosplenial cortex are organized such that the rostral and caudal AD, respectively, project to the caudal and rostral retrosplenial cortex. In contrast, the projections to the presubiculum are not organized topographically. Other minor projections were also observed in the parasubiculum and part of the medial entorhinal area. These results indicate that the AD provides strong projections to the retrosplenial cortex and presubiculum, suggesting that these projections constitute essential pathways to these cortical regions for transmitting mnemonic information, such as a novel conditioning stimulus during the initial stage of avoidance learning.

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats

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.

Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline

The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline produced a clear impairment in the IA task. In animals exposed only to the apparatus, amitriptyline decreased CO activity in nine brain regions, without affecting the remaining regions. In animals that underwent the IA training phase, amitriptyline reduced CO activity in only three of these nine regions. In animals treated with saline, IA acquisition increased CO activity in the medial prefrontal cortex, the prelimbic cortex, and the medial mammillary body, and diminished it in the medial septum and the nucleus basalis of Meynert with respect to animals exposed only to the IA apparatus. In animals treated with amitriptyline, IA acquisition did not modify CO activity in any of these regions, but increased it in the anteromedial nucleus of the thalamus, the diagonal band of Broca, and the dentate gyrus. The results reveal a pattern of changes in brain oxidative metabolism induced by IA training in saline-treated animals that was clearly absent in animals submitted to the same behavioural training but treated with amitriptyline.