Basolateral amygdala lesions in the rat produce an abnormally persistent latent inhibition with weak preexposure but not with context shift

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its nonreinforced preexposure. We have recently reported that basolateral amygdala (BLA) lesions lead to an abnormally persistent LI under conditions that normally disrupt LI, namely, extended conditioning. This study tested whether BLA lesions would induce abnormally persistent LI under two additional conditions disrupting LI in controls, namely, context shift and weak preexposure. LI was measured in an active avoidance procedure. In the first experiment, rats received 100 nonreinforced preexposures and were conditioned either in the same or in a different context from that of the preexposure stage. In the second experiment, rats received 50 nonreinforced preexposures and were conditioned in the same context as that of preexposure. Sham-operated rats showed LI in the same but not in the different context condition or with low number of preexposures. BLA lesions produced abnormally persistent LI with low number of preexposures but not with context shift. It is suggested that the BLA is involved in LI modulation based on the impact of preexposure and conditioning but not on contextual information.     

Latent inhibition is disrupted by nucleus accumbens shell lesion but is abnormally persistent following entire nucleus accumbens lesion: The neural site controlling the expression and disruption of the stimulus preexposure effect

Latent inhibition (LI) is the proactive interference of repeated nonreinforced preexposure to a stimulus with subsequent performance on a learning task involving that stimulus. The present experiments investigated the role of the nucleus accumbens (NAC) in LI. LI was measured in a thirst motivated conditioned emotional response procedure with low or high number of conditioning trials, and in two-way active avoidance procedure with the stages of preexposure and conditioning taking place in the same or different contexts. Sham-lesioned rats showed LI with low but not high number of conditioning trials and if preexposure and conditioning took place in the same context but not if the context was changed between the stages. Lesion to the shell subregion of the NAC disrupted LI but LI was preserved in rats with a combined lesion to the NAC shell and core subregions. Moreover, rats with a combined shell-core lesion persisted in showing LI in spite of high number of conditioning trials and in spite of context change. These results show that the NAC is not essential for the acquisition of LI but rather plays a key role in regulating the expression of LI. Moreover, they suggest that the two subregions of the NAC contribute competitively and cooperatively to this process, selecting the response appropriate to the stimulus-no event or the stimulus-reinforcement association in conditioning.     

The effects of state of consciousness and latent inhibition on hippocampal unit activity in the rat during conditioning

The activity of single cells in rat hippocampus was monitored in animals given 15 to 20 nonreinforced tone presentations prior to the administration of tone-shock pairings and in rats receiving no tone preexposure prior to aversive training. Tones were presented during both slow wave sleep and quiet waking. A reduction in hippocampal activity was seen to tones presented to the sleeping animal in the preexposed group. In addition, tones presented to waking animals enhanced activity in cells from the nonpreexposed group while having little effect on those in the preexposed group. Results are discussed in terms of attentional and stimulus salience models of hippocampal function.     

The latent inhibition model of schizophrenic attention disorder. Haloperidol and sulpiride enhance rats' ability to ignore irrelevant stimuli

Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning to ignore, or tune out, irrelevant stimuli. Two experiments investigated the effects of haloperidol (0.02, 0.1, and 0.5 mg/kg) and sulpiride (100 mg/kg) administration on LI. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: (1) preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; (2) conditioning, in which the preexposed stimulus was paired with shock; and (3) test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 hr apart. In the preexposure stage, only ten nonreinforced stimulus preexposures were given, a procedure known to be insufficient to yield LI in normal animals. In both experiments, LI was indeed absent in the placebo animals. In marked contrast, animals treated with haloperidol (experiment 1) as well as with sulpiride (experiment 2) exhibited LI. These results demonstrate that both typical and atypical neuroleptics enhance animals' capacity to ignore irrelevant stimuli. The implications of this finding for an animal model of schizophrenia and for a novel screening test for antipsychotic drugs are discussed.     

Spatio-temporal distribution of conditioned evoked potentials during latent inhibition in the cat

Using the model of shortly delayed defensive conditioned reflexes in cats it is shown that nonreinforced preexposure of conditioned stimulus leads to a definite manifestation of electrographic correlates of the memory trace, i. e. of the conditioned evoked potential in examined brain structures, as well as of conditioned neurographic response and conditioned skin-galvanic reaction. The reproduction of the conditioned evoked potentials was completely blocked in the cortex and zona incerta. The conditioned neurographic response was blocked too. The probability of skin-galvanic reaction appearance was harshly decreased.     

Effect of septal lesions on male song and aggression in the colonial zebra finch (Taeniopygia guttata) and the territorial field sparrow (Spizella pusilla)

The present investigation assessed the effect of lesions of the septum on male courtship and aggression in the territorial field sparrow (Spizella pusilla) and the colonial zebra finch (Taeniopygia guttata). In addition, pair-bonding and a variety of other social behaviors were examined in the zebra finch and dawn song (both the strictly agonistic song type and the multipurpose song type) was examined in the field sparrow. Zebra finches were tested in three phases both before and after receiving bilateral electrolytic lesions of the septum or sham surgery. These phases were: (1) competition tests in which a subject and a stimulus male were exposed to a female in an adjacent cage; (2) sexual behavior tests with a female; and (3) 10-day group cage tests in which subjects were in a mixed-sex environment. Aggressive behaviors (chases, threats, beak fences and pecks) were significantly reduced by septal lesions but not by sham surgery. Directed song (courtship) was significantly reduced in sexual behavior tests, with similar trends in other testing phases. Male field sparrows were tested 2 days pre-surgery and 2 days post-surgery in outdoor aviaries placed in their natural habitat. Tests consisted of dawn song observations and observations of courtship and aggression following introduction of a female to the subject's aviary, which was followed 10 min later by the introduction of another male (without removing the female). Septal lesions significantly facilitated both overt aggression (chases) and the number of simple (multi-purpose) songs. These results provide evidence that the septum participates in the regulation of male aggression and song in songbirds, and further suggest that variations in septal function may exist between territorial and colonial species.     

Facilitation of learning by post-trial injection of substance P into the medial septal nucleus

The undeca-neuropeptide substance P (SP) was injected post-trial into the medial nucleus of the septum to test its influence on passive avoidance learning in rats. A facilitation of learning was attained in the alcove avoidance task with doses of 50 ng (37 pmol), 500 ng (370 pmol) and 6.7 μg (5 nmol) SP and in the step-up avoidance task with 500 ng and 6.7 μg SP. In the step-down avoidance task no influence of SP was discernible, probably as a consequence of the high retention shown by control animals, masking a possible SP-induced facilitation of learning (ceiling effect). Interestingly, in its effect on learning, SP applied in the septum imitates the effect of electrical septal stimulation, thus providing another example for the parallelism between post-trial SP and electrical brain stimulation which we have demonstrated previously in the substantia nigra, amygdala and lateral hypothalamus.     

Electrolytic lesions of the medial septum enhance latent inhibition in a conditioned taste aversion paradigm

The effects of medial septal lesions on latent inhibition (LI) were assessed in a conditioned taste aversion paradigm. Animals were tested in a LI paradigm 2 weeks after receiving medial septal or sham lesions. The LI paradigm involved a pre-exposure phase in which water-deprived rats were allowed access to either water (non-pre-exposed; NPE) or 5% sucrose (pre-exposed; PE), followed by a conditioning phase in which animals were allowed access to sucrose and subsequently injected with lithium chloride, and a test phase in which animals were allowed access to both sucrose and water. LI was assessed by comparing the %-sucrose consumed in PE and NPE groups on the test day. There was a significantly greater LI effect in the lesion group than in the sham group, suggesting that electrolytic lesions to the medial septum can enhance LI in a CTA paradigm.     

Distribution of enkephalin, substance P, tyrosine hydroxylase, and 5-hydroxytryptamine immunoreactivity in the septal region of the rat

Immunocytochemical methods were used to define the distribution of enkephalin (ENK), substance P (SP), tyrosine hydroxylase (TH), and serotonin (5-hydroxytryptamine: 5HT) in the rat septum. A dense plexus of axons containing enkephalin-like immunoreactivity is found in the intermediate lateral septal nucleus. This is surrounded laterally by SP-containing cell bodies and axons and medially by ENK-containing cell bodies. Both SP- and ENK-immunoreactive axons form pericellular and peridendritic terminal arbors around lateral septal neurons. TH-positive axons are distributed throughout the septum and form dense pericellular terminal baskets around scattered neurons in the medial half of the intermediate lateral septal nucleus and in the extreme lateral septum. Very few SP and TH immunoreactive axons are present in the ENK immunoreactive plexus zone. 5HT-immunoreactive axons are most dense at the lateral edge of the ventral and intermediate lateral septal nuclei but form pericellular terminal arbors only in the dorsal lateral septal nucleus, in the septofimbrial nucleus, and in the dorsal cap of the medial septal nucleus. These results indicate that the dorsal and intermediate lateral septal nuclei include three histochemically distinct laminated subfields: (1) an ENK immunoreactive axonal plexus within the lateral aspect of the intermediate lateral septal nucleus, (2) a more medial region of scattered ENK immunoreactive perikarya and similarly scattered TH immunoreactive pericellular baskets, and (3) a dorsolateral zone occupied by SP neurons and 5HT-containing pericellular baskets. Thus, the data suggest that SP- and ENK-containing neuronal populations in the lateral septum receive different monoaminergic inputs. Further, the somewhat exclusive laminated pericellular termination of peptide- and catecholamine-containing axons in the lateral septum predicts very different functional and pharmacological properties among zones.     

Context-US learning in Aplysia californica

Two experiments explored learning about the relation between an unconditioned stimulus (US) and the context in which that US was delivered in Aplysia californica. Subjects were exposed to 2 different contexts. They received a series of moderate electric shock USs in one context but not in the other. Experiment 1 revealed that the context-shock pairings were sufficient to establish an association between that context and the shock. That association was demonstrated by the ability of the reinforced context to enhance a defensive reflex and to reduce learning about a conditioned stimulus (CS) that was subsequently paired with the shock US. Experiment 2 provided evidence that the context-US association could be extinguished by simple nonreinforced exposure to the reinforced context. These results show that context conditioning is not unique to vertebrate learning. We argue that this learning is difficult to accommodate within current contiguity-based neuronal models of learning.     

Development of the hippocamposeptal projection in the rat

We analyzed the development of the hippocamposeptal projection and the morphology of the neurons giving rise to this projection. The fluorescent tracer Dil was injected into the septal region or the hippocampus in fixed brains of embryonic and early postnatal rats. Anterogradely labeled hippocampal axons first reached the septal region at E16. They ran along the midline of the brain, thereby approaching the medial septum. Axons to the lateral septum were first observed around E18/19. The lateral septum is partly innervated by collaterals of axons that travel to the medial septum. The projection to the lateral septal nuclei becomes more massive during early postnatal stages, whereas that to the medial septum becomes smaller. Cells in the medial septum retrogradely labeled by injection into the hippocampus were first observed at E18. Thus, the hippocamposeptal projection is established earlier than the septohippocampal projection. The first hippocampal projection neurons are nonpyramidal neurons that appear to pioneer the pathway to the septum. Pyramidal cell axons follow this first cohort of axons into the medial septum. Pyramidal cells could be retrogadely labeled from the medial septum during the perinatal period but then diminished in number. At P10, only nonpyramidal cells were labeled by medial septal injections. This indicates that the pyramidal component of this projection is transient and is removed shortly after birth. However, as is known from ther studies, hippocampal pyramidal cells give rise to a powerful projection to the lateral septum in adult animals. Our results show that there is a considerable remodeling of the projection from the hippocampus to the septum during ontogenetic development. © 1995 Willy-Liss, Inc.     

Mapping of sensory-responsive cells in the septal area of the rat

A study of sensory-responsive characteristics of single cells of the septal area of male rats was undertaken to determine the distribution of stimulation-induced changes in septal activity. Single cells were systematically sampled in six planes transecting the rostral-caudal axis of the septal area and were tested for responsiveness to visual, auditory, tactual, gustatory and olfactory stimuli. Approximately 50% of the sampled population of septal cells was responsive to at least one stimulus. Most of the responses of septal cells to stimulation were excitatory and occurred at the onset of stimulation. Regions of concentration of sensory-responsi veness cells in the system were found to lie in medial areas of the septum consisting of the dorsomedial portion of the lateral septal nucleus, the medial septal nucleus and the ventral portions of the medial and lateral nuclei. Visual, auditory and tactual stimuli were most effective in producing changes in spontaneous activity of units in these regions. On the basis of relationships of the medial septal region to other limbic areas having sensory-responsive properties, it is concluded that the medial septal area is one component of a limbic sensory system.     

Two distinct populations of cholinergic neurons in the septum of raccoon (Procyon lotor): evidence for a separate subset in the lateral septum.

The present study focused on cholinergic neurons in the lateral septal region of the raccoon detected by choline acetyltransferase (ChAT)-immunostaining. For comparison of the cholinergic neurons of the medial and lateral septal nuclei, soma sizes were measured, and several antibodies were applied that differentially characterize these cells in several species: low-affinity neurotrophin receptor p75 (p75(NTR)), calbindin-D(28k) (CALB), and constitutive nitric oxide synthase (cNOS). To compare the basic organization of the raccoon septum with that in other mammals, parvalbumin (PARV) immunocytochemistry and Wisteria floribunda-agglutinin (WFA) lectin histochemistry also were used in double-staining experiments. The ChAT-immunoreactive neurons of the rostral lateral septum are arranged in laminae. Accumulations of cholinergic varicosities, often clearly ensheathing noncholinergic neurons, occupy small territories of the rostral septum. Such regions become larger in the caudal septum. They are assumed to correspond to the septohippocampal and septofimbrial nuclei of the rat. In contrast to the large medial septal cholinergic neurons of the raccoon that contain p75(NTR), CALB, and cNOS, the cholinergic neurons of the lateral septum are smaller and do not express these markers. A further peculiarity is that the region of the lateral septum that contains cholinergic neurons corresponds to WFA-labelled extracellular matrix zones that contain chondroitin sulfate proteoglycans. In addition to clustered thread- or ring-like accumulations of the WFA, sparsely labelled perineuronal nets surround the lateral septal cholinergic neurons. Similar to other species that have been investigated, perineuronal nets are completely absent around cholinergic cells of the medial septum. The PARV-containing neurons of this region, however, are enwrapped by perineuronal nets as they are in the rat. Within the medial septum, the PARV-containing neurons are restricted to ventral bilateral territories that are devoid of cholinergic cells. In this respect, they differ from the more vertically arranged PARV-containing medial septal cells in rodents and primates. Apart from striking differences in numbers and distribution patterns, the raccoon lateral septal cholinergic neurons resemble those detected by Kimura et al. (Brain Res [1990] 533:165-170) in the ventrolateral septal region of rat and monkey. Their participation in the functions of the lateral septum remains to be elucidated.     

Septal arginine vasopressin (AVP) receptor regulation in rats depleted of septal AVP following long-term castration

Arginine vasopressin (AVP) causes severe motor disturbances, including barrel rotations and myotonic/myoclonic convulsions, following repeated injections into either a lateral cerebral ventricle or the ventral septal area (VSA) of the rat brain. Because the AVP content of the rat septal area has been shown to be virtually eliminated following long-term castration, and because removal of a receptor ligand typically results in receptor upregulation and behavioral supersensitivity to the ligand, we tested the hypothesis that long-term castrated rats may be supersensitive to the motor actions caused by centrally injected AVP and may have upregulated septal AVP receptors. In these experiments, adult male Wistar rats were used 5 months after castration or, as controls, after sham castration. The effectiveness of long-term castration in eliminating AVP content of the VSA was indicated by the observation that a priming hypertonic saline stimulus (known to induce the central release of AVP and sensitize the rat brain) sensitized the brains of sham control rats but not of the castrated rats to the motor actions of a subsequent intracerbroventricular injection of AVP. The motor actions of centrally injected AVP, as well as septal AVP receptor characteristics (number and affinity), and AVP-stimulated phosphoinositide (PI) hydrolysis were then investigated in long-term castrated and sham control rats. Motor disturbances induced by either a first or a second injection of AVP were not greater in long-term castrated rats than in sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠脑中隔核毁损对关联性条件化恐惧的影响

目的：中隔核(Septum)在实验大鼠对关联性刺激所产生的条件化恐惧的获得(Acquisi-tion)已经证明具有重要的作用，但对关联性刺激所产生的条件化恐惧的表达(Expression)的作用至今仍未阐明。方法：实验组大鼠分别采用射频(Radiofrequency)技术对双侧中隔核区行组织毁损术，对照组大鼠完全按照实验组大鼠的手术程序，但不采用射频技术进行组织破坏，然后均接受经典的条件化恐惧的实验训练。实验1：实验大鼠(n=18)在手术后第11d，经采用足部电击(Footshocks)方法产生与之关联的条件化恐惧，然后在24h后，在相同条件下但不予以足部电击的情况下评定其僵滞(Freezing)行为；实验2：实验大鼠(n=16)在手术前24h，先采用足部电击方法产生与之关联的条件化恐惧，然后在手术后第11d在相同条件下但不予以足部电击的情况下评定僵滞行为。结果:在训练前接受双侧中隔核毁损的大鼠既不阻断也不增强关联性条件化僵滞，而在训练后接受双侧中隔核毁损的大鼠则明显阻断关联性条件化僵滞的表达，同时因关联性条件化恐惧所致非粪的数量也明显减少。结论:双侧中隔核的毁损并不引起关联性条件化恐惧的增强，而是明显减弱关联性条件化恐惧的表达水平，因此，中隔核具有潜在增强关联性条件化恐惧的表达的作用。     

Septal unit activity during classical conditioning: a regional comparison

Single unit activity was recorded from the lateral and medial septum of rats during aversive Pavlovian differential conditioning. One conditioned stimulus (CS+) was consistently paired with and another (CS-) was explicitly unpaired with a brief shock unconditioned stimulus (US). In the lateral septum single unit activity generally increased in the presence of a conditioned inhibitor of fear (CS-), while unit activity generally decreased in the presence of a conditioned excitor of fear (CS+). Responses in the medial septum were more heterogeneous. Many cells did not show plastic changes to the CSs, others showed responses to the conditioned stimuli opposite to that seen in the lateral septum. A small group of cells showed responses similar to that seen in the lateral septum. Finally, theta bursting cells were seen in the medial septum with some evidence of increased theta activity in the presence of a conditioned inhibitor of fear (CS-). The results were interpreted as consistent with the proposition that the lateral septum mediates the inhibition of aversive emotional states. The medial septum may have some involvement with the activation of fear or anxiety.     

Archistriatal Lesions Impair the Acquisition of Filial Preferences During Imprinting in the Domestic Chick

The avian archistriatum has been demonstrated to play a role in agonistic behaviours and avoidance learning. However, the extent of its role in learning is unknown. The involvement of the archistriatum in the learning process of filial imprinting was therefore investigated in day-old chicks. Bilateral archistriatal lesions, lateral cerebral area lesions or sham archistriatal penetrations were made in dark-reared, day-old chicks, which were subsequently exposed to either a rotating red box or blue cylinder for 2 × 1 h training sessions. Three hours later, the approach of chicks to their training object and to the other, novel object was measured. Chicks with archistriatal lesions ran a similar distance towards each stimulus and therefore failed to display a preference for their training object. However, chicks with sham archistriatal penetrations or lateral cerebral area lesions exhibited a significant preference for the object they had been trained upon. These results demonstrate that the archistriatum is essential for the expression of an imprinted preference. All chicks approached their training object significantly more on their second compared to their first training exposure, suggesting that some aspects of imprinting behaviour remain intact in chicks with archistriatal lesions. Taken together with the results of previous work, the current data suggest that the archistriatum may be involved in retention of significant aspects of the imprinting experience, or in motivation to approach imprinting objects.     

Tactile stimulation activates dopamine release in the lateral septum

Little is known about the functional properties of the dopamine innervation of the lateral septum. In this study, the feasibility of using microdialysis to assess action-potential mediated release of dopamine in the lateral septum was established. A mild stressor, in the form of handling, significantly increased septal dopamine levels, implicating a role for dopamine in sensory-related processing associated with the septal complex.     

Catecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in rats

The performance of rats on the conditioned blocking test of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA)-depleting lesions of the frontal cortex, septum and ventral tegmental area (VTA). Animals were trained on two sessions with tone and/or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ratio (avoidance to b/a + b) and response latencies. No deficits were recorded on tests of sensory and motor ability. The VTA group alone showed a hyperlocomotor response to apomorphine treatment and did not acquire the avoidance response. The appearance of blocking in the septal group was delayed until the end of the test session. Blocking was mildly attenuated in the frontal group. DA levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20 and 50% in frontal and septal areas. This suggests that the level of DA activity or the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and/or the normal ability of rats not to attend to a redundant stimulus.