Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats.

Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.

Pathways from the Superior Colliculus to the Basal Ganglia.

The present work aims to review the structural organization of the mammalian superior colliculus (SC), the putative pathways connecting the SC and the basal ganglia, and their role in organizing complex behavioral output. First, we review how the complex intrinsic connections between the SC's laminae projections allow for the construction of spatially aligned, visual-multisensory maps of the surrounding environment. Moreover, we present a summary of the sensory-motor inputs of the SC, including a description of the integration of multi-sensory inputs relevant to behavioral control. We further examine the major descending outputs toward the brainstem and spinal cord. As the central piece of this review, we provide a thorough analysis covering the putative interactions between the SC and the basal ganglia. To this end, we explore the diverse thalamic routes by which information from the SC may reach the striatum, including the pathways through the lateral posterior, parafascicular, and rostral intralaminar thalamic nuclei. We also examine the interactions between the SC and subthalamic nucleus, representing an additional pathway for the tectal modulation of the basal ganglia. Moreover, we discuss how information from the SC might also be relayed to the basal ganglia through midbrain tectonigral and tectotegmental projections directed at the substantia nigra compacta and ventrotegmental area, respectively, influencing the dopaminergic outflow to the dorsal and ventral striatum. We highlight the vast interplay between the SC and the basal ganglia and raise several missing points that warrant being addressed in future studies.

Predator fear memory depends on glucocorticoid receptors and protein synthesis in the basolateral amygdala and ventral hippocampus.

Previous studies have suggested that the basolateral amygdala (BLA) and the ventral hippocampus (VH) are critical sites for predator-related fear memory. Predator exposure is an intense emotional experience and should increase plasmatic corticosterone likely to modulate the emotion-related memories. However, it is unclear whether the BLA and VH harbor plastic events underlying predator-related fear memory storage and how molecular and endocrine mechanisms interact to modulate memory to the predatory threat. Here, we first examined the effects of protein synthesis inhibition in the BLA and VH on fear memory to a predatory threat. We next evaluated how exposure to a predatory threat impacts the corticosterone release and how the inhibition of corticosterone synthesis can influence predator-related fear memory. Finally, we examined how predator exposure triggers the activation of glucocorticoid and mineralocorticoid receptors in the BLA and VH and whether the GR antagonist injection affects predator-related fear memory. We showed that predator-related contextual fear is dependent on protein synthesis in the BLA and VH. Moreover, we described the impact of rapid glucocorticoid release during predatory exposure on the formation of contextual fear responses and that GR-induced signaling facilitates memory consolidation within the BLA and VH. The results are relevant in understanding how life-threatening situations such as a predator encounter impact fear memory storage and open exciting perspectives to investigate GR-induced proteins as targets to deciphering and manipulating aversive memories.

The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats.

Predator exposure is a life-threatening experience and elicits learned fear responses to the context in which the predator was encountered. The anterior cingulate area (ACA) occupies a pivotal position in a cortical network responsive to predatory threats, and it exerts a critical role in processing fear memory. The experiments were made in mice and revealed that the ACA is involved in both the acquisition and expression of contextual fear to predatory threat. Overall, the ACA can provide predictive relationships between the context and the predator threat and influences fear memory acquisition through projections to the basolateral amygdala and perirhinal region and the expression of contextual fear through projections to the dorsolateral periaqueductal gray. Our results expand previous studies based on classical fear conditioning and open interesting perspectives for understanding how the ACA is involved in processing contextual fear memory to ethologic threatening conditions that entrain specific medial hypothalamic fear circuits.

Defensive behaviors and brain regional activation changes in rats confronting a snake.

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

The rostrodorsal periaqueductal gray influences both innate fear responses and acquisition of fear memory in animals exposed to a live predator.

A few studies have evaluated the behavioral roles of the periaqueductal gray (PAG) in animals facing ethologically relevant threats. Exposure to a live cat induces striking activation in the rostrodorsal and caudal ventral PAG. In the present investigation, we first showed that cytotoxic lesions of the rostrodorsal and caudal ventral PAG had similar effects on innate fear responses during cat exposure, practically abolishing freezing and increasing risk assessment responses. Conversely, rostrodorsal PAG lesions but not caudal ventral lesions disrupted learned contextual fear responses to cat exposure. Next, we examined how muscimol inactivation of the rostrodorsal PAG at different times (i.e., during, immediately after and 20 min after cat exposure) influences learned contextual fear responses, and we found that inactivation of the rostrodorsal PAG during or immediately after cat exposure but not 20 min later impaired contextual fear learning. Thus, suggesting that the rostrodorsal PAG is involved in the acquisition, but not the consolidation, of contextual fear memory to predatory threat. Notably, the dosolateral PAG contains a distinct population of neurons containing the neuronal nitric oxide synthase (nNOS) enzyme, and in the last experiment, we investigated how nitric oxide released in rostrodorsal PAG influences contextual fear memory processing. Accordingly, injection of a selective nNOS inhibitor into the rostrodorsal PAG immediately after cat exposure disrupted learned contextual responses. Overall, the present findings suggest that the acquisition of contextual fear learning is influenced by an optimum level of dorsal PAG activation, which extends from during to shortly after predator exposure and depends on local NO release.

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.

Roles of the anterior basolateral amygdalar nucleus during exposure to a live predator and to a predator-associated context.

The basolateral amygdala complex, which includes the lateral, basolateral and basomedial nuclei, has been implicated in innate and contextual fear responses to predator threats. In the basolateral complex, the lateral and posterior basomedial nuclei are able to process predator odor information, and they project to the predator-responsive hypothalamic circuit; lesions in these amygdalar sites reduce innate responses and practically abolish contextual fear responses to predatory threats. In contrast to the lateral and posterior basomedial nuclei, the basolateral nucleus does not receive direct information from predator olfactory cues and has no direct link to the predator-responsive hypothalamic circuit. No attempt has previously been made to determine the specific role of the basolateral nucleus in fear responses to predatory threats, and we currently addressed this question by making bilateral N-methyl-D-aspartate lesions in the anterior basolateral nucleus of the amygdala (BLAa), which is often regarded as being contiguous with the lateral amygdalar nucleus, and tested both innate and contextual fear in response to cat exposure. Accordingly, BLAa lesions decreased both innate and contextual fear responses to predator exposure. Considering the targets of the BLAa, the nucleus accumbens appears to be a potential candidate to influence innate defensive responses to predator threats. The present findings also suggest that the BLAa has a role in fear memory of predator threat. The BLAa is likely involved in memory consolidation, which could potentially engage BLAa projection targets, opening interesting possibilities in the investigation of how these targets could be involved in the consolidation of predator-related 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.

On the verge of a respiratory-type panic attack: Selective activations of rostrolateral and caudoventrolateral periaqueductal gray matter following short-lasting escape to a low dose of potassium cyanide.

Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO2, it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxia-sensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO2. Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (>60µg) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-µg KCN (air/KCN), a 2-min exposure to 13% CO2 (CO2/saline), or a combined stimulus (CO2/KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO2 alone was ineffective, it potentiated the KCN-evoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO2/saline and CO2/KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack.

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.

Testing conditions in shock-based contextual fear conditioning influence both the behavioral responses and the activation of circuits potentially involved in contextual avoidance.

Previous studies from our group have shown that risk assessment behaviors are the primary contextual fear responses to predatory and social threats, whereas freezing is the main contextual fear response to physically harmful events. To test contextual fear responses to a predator or aggressive conspecific threat, we developed a model that involves placing the animal in an apparatus where it can avoid the threat-associated environment. Conversely, in studies that use shock-based fear conditioning, the animals are usually confined inside the conditioning chamber during the contextual fear test. In the present study, we tested shock-based contextual fear responses using two different behavioral testing conditions: confining the animal in the conditioning chamber or placing the animal in an apparatus with free access to the conditioning compartment. Our results showed that during the contextual fear test, the animals confined to the shock chamber exhibited significantly more freezing. In contrast, the animals that could avoid the conditioning compartment displayed almost no freezing and exhibited risk assessment responses (i.e., crouch-sniff and stretch postures) and burying behavior. In addition, the animals that were able to avoid the shock chamber had increased Fos expression in the juxtadorsomedial lateral hypothalamic area, the dorsomedial part of the dorsal premammillary nucleus and the lateral and dorsomedial parts of the periaqueductal gray, which are elements of a septo/hippocampal-hypothalamic-brainstem circuit that is putatively involved in mediating contextual avoidance. Overall, the present findings show that testing conditions significantly influence both behavioral responses and the activation of circuits involved in contextual avoidance.

Effect of intrahippocampal administration of anti-melanin-concentrating hormone on spatial food-seeking behavior in rats.

Melanin-concentrating hormone (MCH) is a hypothalamic peptide that plays a critical role in the regulation of food intake and energy metabolism. In this study, we investigated the potential role of dense hippocampal MCH innervation in the spatially oriented food-seeking component of feeding behavior. Rats were trained for eight sessions to seek food buried in an arena using the working memory version of the food-seeking behavior (FSB) task. The testing day involved a bilateral anti-MCH injection into the hippocampal formation followed by two trials. The anti-MCH injection did not interfere with the performance during the first trial on the testing day, which was similar to the training trials. However, during the second testing trial, when no food was presented in the arena, the control subjects exhibited a dramatic increase in the latency to initiate digging. Treatment with an anti-MCH antibody did not interfere with either the food-seeking behavior or the spatial orientation of the subjects, but the increase in the latency to start digging observed in the control subjects was prevented. These results are discussed in terms of a potential MCH-mediated hippocampal role in the integration of the sensory information necessary for decision-making in the pre-ingestive component of feeding behavior.

Restraint stress and social defeat: What they have in common.

Bob Blanchard was a great inspiration for our studies on the neural basis of social defense. In the present study, we compared the hypothalamic pattern of activation between social defeat and restraint stress. As important stress situations, both defeated and immobilized animals displayed a substantial increase in Fos in the parvicellular part of the paraventricular nucleus,mostly in the region that contains the CRH neurons. In addition, socially defeated animals, but not restrained animals, recruited elements of the medial hypothalamic conspecific-responsive circuit, a region also engaged in other forms of social behavior. Of particular interest, both defeated and immobilized animals presented a robust increase in Fos expression in specific regions of the lateral hypothalamic area (i.e., juxtaparaventricular and juxtadorsomedial regions) likely to convey septo-hippocampal information encoding the environmental boundary restriction observed in both forms of stress, and in the dorsomedial part of the dorsal premammillary nucleus which seems to work as a key player for the expression of, at least, part of the behavioral responses during both restraint and social defeat. These results indicate interesting commonalities between social defeat and restraint stress, suggesting, for the first time, a septo-hippocampal­hypothalamic path likely to respond to the environmental boundary restriction that may act as common stressor component for both types of stress. Moreover, the comparison of the neural circuits mediating physical restraint and social defense revealed a possible path for encoding the entrapment component during social confrontation.

Periaqueductal gray µ and κ opioid receptors determine behavioral selection from maternal to predatory behavior in lactating rats.

Every mother must optimize her time between caring for her young and her subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a critical site that modulates the switch between maternal and predatory behavior. Opioids play multiple roles in both maternal behavior and this switching process. The present study used a pharmacological approach to evaluate the functional role of rlPAG µ and κ opioid receptors in behavioral selection. Rat dams were implanted with a guide cannula in the rlPAG and divided into three experiments in which we tested the role of opioid agonists (Experiment 1), the influence of µ and κ opioid receptor blockade in the presence of morphine (Experiment 2), and the influence of µ and κ opioid receptor blockade (Experiment 3). After behavioral test, in Experiment 4, we evaluated rlPAG µ and κ receptor activation in all Experiments 1-3. The results showed that massive opioidergic activation induced by morphine in the rlPAG inhibited maternal behavior without interfering with predatory hunting. No behavioral changes and no receptor activation were promoted by the specific agonist alone. However, κ receptor blockade increased hunting behavior and increased the level of µ receptor activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by a functional interaction between opioid receptor subtypes. Such a compensatory receptor interaction appears to be relevant for behavioral selection among motivated behaviors. These findings indicate a role for multiple opioid receptor interactions in the modulation of behavioral selection between maternal and predatory behaviors in the PAG.

NK1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats.

Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1mg/kg) followed 30 min later by saline or PILO (350 mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100 pmol) - an NK1 receptor antagonist - were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head-dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic-like profile induced by PILO in rats evaluated in the EPM test.

The many paths to fear.

Fear is an emotion that has powerful effects on behaviour and physiology across animal species. It is accepted that the amygdala has a central role in processing fear. However, it is less widely appreciated that distinct amygdala outputs and downstream circuits are involved in different types of fear. Data show that fear of painful stimuli, predators and aggressive members of the same species are processed in independent neural circuits that involve the amygdala and downstream hypothalamic and brainstem circuits. Here, we discuss data supporting multiple fear pathways and the implications of this distributed system for understanding and treating fear.

Both the dorsal hippocampus and the dorsolateral striatum are needed for rat navigation in the Morris water maze.

The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum are the core structures of the spatial/relational and stimulus-response (S-R) memory systems, respectively. This theory is supported by double dissociation studies showing that the spatial and cue (S-R) versions of the Morris water maze are impaired by lesions in the dorsal hippocampus and dorsal striatum, respectively. In the present study we further investigated whether adult male Wistar rats bearing double and bilateral electrolytic lesions in the dorsal hippocampus and dorsolateral striatum were as impaired as rats bearing single lesions in just one of these structures in learning both versions of the water maze. Such a prediction, based on the multiple memory systems theory, was not confirmed. Compared to the controls, the animals with double lesions exhibited no improvement at all in the spatial version and learned the cued version very slowly. These results suggest that, instead of independent systems competing for holding control over navigational behaviour, the hippocampus and dorsal striatum both play critical roles in navigation based on spatial or cue-based strategies.

The periaqueductal gray as a critical site to mediate reward seeking during predatory hunting.

Previous studies using morphine-treated dams reported a role for the rostral lateral periaqueductal gray (rlPAG) in the behavioral switching between nursing and insect hunting, likely to depend on an enhanced seeking response to the presence of an appetitive rewarding cue (i.e., the roach). To elucidate the neural mechanisms mediating such responses, in the present study, we first observed how the rlPAG influences predatory hunting in male rats. Our behavioral observations indicated that bilateral rlPAG NMDA lesions dramatically interfere with prey hunting, leaving the animal without chasing or attacking the prey, but do not seem to affect the general levels of arousal, locomotor activity and regular feeding. Next, using Phaseolus vulgaris-leucoagglutinin (PHA-L), we have reviewed the rlPAG connection pattern, and pointed out a particularly dense projection to the hypothalamic orexinergic cell group. Double labeled PHA-L and orexin sections showed an extensive overlap between PHA-L labeled fibers and orexin cells, revealing that both the medial/perifornical and lateral hypothalamic orexinergic cell groups receive a substantial innervation from the rlPAG. We have further observed that both the medial/perifornical and lateral hypothalamic orexinergic cell groups up-regulate Fos expression during prey hunting, and that rlPAG lesions blunted this Fos increase only in the lateral hypothalamic, but not in the medial/perifornical, orexinergic group, a finding supposedly associated with the lack of motivational drive to actively pursue the prey. Overall, the present results suggest that the rlPAG should exert a critical influence on reward seeking by activating the lateral hypothalamic orexinergic cell group.

The role of the ventrolateral caudoputamen in predatory hunting.

The ventrolateral caudoputamen (VLCP) is well known to participate in the control of orofacial movements and forepaw usage accompanying feeding behavior. Previous studies from our laboratory have shown that insect hunting is associated with a distinct Fos up-regulation in the VLCP at intermediate rostro-caudal levels. Moreover, using the reversible blockade with lidocaine, we have previously suggested that the VLCP implements the stereotyped actions seen during prey capture and handling, and may influence the motivational drive to start attacking the roaches, as well. However, considering that (1) lidocaine suppresses action potentials not only in neurons, but also in fibers-of-passage, rendering the observed behavioral effect not specific to the ventrolateral caudoputamen; (2) the short lidocaine-induced inactivation period had left a relatively narrow window to observe the behavioral changes; and (3) that the restriction stress to inject the drug could have also disturbed hunting behavior, in the present study, we have examined the role of the VLCP in predatory hunting by placing bilateral NMDA lesions three weeks previous to the behavior testing. We were able to confirm that the VLCP serves to implement the stereotyped sequence of actions seen during prey capture and handling, but the study did not confirm its role in influencing the motivational drive to hunt. Together with other studies from our group, the present work serves as an important piece of information that helps to reveal the neural systems underlying predatory hunting.