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Biomedical subjects

M S Fanselow

Publications and source records attributed to M S Fanselow.

At least 37 records · Page 2Linked to original sources
PubMed1998

Appetitive motivational states differ in their ability to augment aversive fear conditioning in rats (Rattus norvegicus).

The present experiments compared the effects of 2 appetitive motivational states on the acquisition of Pavlovian fear conditioning in rats (Rattus norvegicus). In Experiment 1, rats were deprived of either water or food prior to contextual fear conditioning, which consisted of the delivery of a single footshock in a novel observation chamber. Conditional fear to the contextual cues of the conditioning chamber was measured by observing freezing behavior. The results revealed that water, but not food, deprivation enhanced conditional freezing to contextual stimuli paired with footshock. Experiment 2 indicated that the different impact of food or water deprivation on the acquisition of conditional freezing was not due to differential generalization decrements during extinction testing. Together, these experiments suggest that the modulation of fear conditioning by deprivation state is specific to certain motivational systems.

Animals↗
PubMed1998

Differential effects of neurokinin-1 receptor activation in subregions of the periaqueductal gray matter on conditional and unconditional fear behaviors in rats.

Central neurokinin-1 (NK-1) receptors are thought to modulate aversion, whereas the periaqueductal gray matter (PAG) is a common pathway for the integration of fear behaviors. The authors determined whether injection of an NK-1 agonist (GR73632) into subregions of the PAG would alter fear-related behaviors. Behavioral inactivity was increased by GR73632 injected into the caudodorsal PAG or the dorsal raphe. Flight behavior induced by stimulation of the dorsal PAG or by a footshock was decreased after injection of GR73632 into the dorsal PAG. Rats that had 6 pairings of a tone with a footshock after injection of GR73632 into the dorsal PAG displayed more freezing behavior than controls at the beginning of the session. However, there was no change in the shock- or the tone-induced freezing because some GR73632-treated rats, but no controls, froze during the baseline period. It is concluded that NK-1 receptors in the dorsal PAG modulate the unconditional but not the mnemonic aspects of fear behaviors.

Acoustic Stimulation↗
PubMed1997

Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice.

Mice deficient in monoamine oxidase A (MAOA), an enzyme that metabolizes monoamines such as norepinephrine and serotonin, have elevated norepinephrine and serotonin levels in the frontal cortex, hippocampus, and cerebellum, compared with normal wild-type mice. Since monoamines in these areas are critically involved in a variety of behaviors, we examined learning and memory (using emotional and motor tasks) in MAOA mutant mice. The MAOA-deficient mice exhibited significantly enhanced classical fear conditioning (freezing to both tone and contextual stimuli) and step-down inhibitory avoidance learning. In contrast, eyeblink conditioning was normal in these mutant mice. The female MAOA-deficient mice also displayed normal species-typical maternal behaviors (nesting, nursing, and pup retrieval). These results suggest that chronic elevations of monoamines, due to a deletion of the gene encoding MAOA, lead to selective alterations in emotional behavior.

Animals↗
PubMed1997

Electrolytic lesions of the fimbria/fornix, dorsal hippocampus, or entorhinal cortex produce anterograde deficits in contextual fear conditioning in rats.

Recent data indicate that dorsal hippocampal (DH) lesions disrupt Pavlovian fear conditioning to contextual cues in rats. In the present study, we examined the effects of electrolytic lesions of the fimbria/fornix (FX) or entorhinal cortex (EC), the primary afferent projection systems to the DH, on contextual fear conditioning in rats. Conditioning consisted of the delivery of unsignaled footshocks in a novel observation chamber, and freezing served as the measure of conditional fear. Electrolytic lesions of the FX, DH, or EC made 1 week before training produced anterograde impairments in both immediate postshock freezing on the conditioning day and freezing during the context extinction test 24 h following training. The deficits in conditional freezing produced by FX, DH, and EC lesions were not statistically different, although the deficits in rats with FX or EC lesions tended to be more severe than those in rats with DH lesions. In addition to producing deficits in conditional freezing, FX, DH, or EC lesions produced a pronounced locomotor hyperactivity. Within the lesion and sham groups, however, locomotor activity was not significantly correlated with conditional freezing. These results indicate that contextual fear deficits in rats with hippocampal formation damage are equivalent following either FX, DH, or EC lesions. The relationship of freezing deficits and locomotor hyperactivity in rats with hippocampal formation lesions is discussed.

Animals↗
PubMed1997

Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats.

Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.

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PubMed1996

Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient.

The role of the basolateral amygdala (LA) in the acquisition and expression of Pavlovian fear conditioning was examined in 80 rats. Excitotoxic lesions were made in the BLA using N-methyl-D-aspartate 7 days before or 1, 14, or 28 days after Pavlovian fear conditioning. Conditioning consisted of three pairings of a tone with an aversive footshock in a novel chamber, and freezing behavior served as an index of conditional fear. BLA lesions abolished conditional freezing to both the contextual and acoustic conditional stimuli at all training-to-lesion intervals, and the magnitude of the impairment did not vary as a function of the training-to-lesion interval. Reacquisition training elevated levels of freezing in rats with BLA lesions but did not reduce the magnitude of their deficit in relation to that of controls. These results reveal that neurons in the BLA have an enduring role in the expression of conditional fear.

Amygdala↗
PubMed1996

N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats.

Three experiments examined the effects of intra-amygdaloid infusions of an N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), on contextual fear conditioning in rats. In Experiment 1, APV infusion into the basolateral amygdala (BLA), before training, disrupted the acquisition of contextual fear. In Experiment 2, APV produced a disruption of both the acquisition and expression of contextual fear. This blockade of contextual fear was not state dependent, not due to a shift in footshock sensitivity, and not the result of increased motor activity in APV-treated rats. In Experiment 3, fear conditioning was not affected by a posttraining APV infusion into the BLA. These results indicate that NMDA receptors in the BLA are necessary for both the acquisition and expression of Pavlovian fear conditioning to contextual cues in rats.

2-Amino-5-phosphonovalerate↗
PubMed1995

Scopolamine selectively disrupts the acquisition of contextual fear conditioning in rats.

Muscarinic cholinergic antagonism produces learning and memory deficits in a variety of hippocampal-dependent tasks. Hippocampal lesions produce both acquisition deficits and retrograde amnesia for contextual fear conditioning, but do not impact fear conditioning to discrete cues. In order to examine the effects of muscarinic antagonism in this paradigm, rats were given scopolamine (1 mg/kg) either before or for 3 days after a Pavlovian fear-conditioning session in which tones were paired with aversive footshocks. Fear to the context and the tone was assessed by measuring freezing in separate tests. It ws found that pretraining, but not posttraining, scopolamine severely impaired contextual fear conditioning; tone conditioning was not affected under either condition (cf., Young, Bohenek, & Fanselow, Neurobiology of Learning and Memory, 63, 174-180, 1995).

Animals↗
PubMed1995

Scopolamine impairs acquisition and facilitates consolidation of fear conditioning: differential effects for tone vs context conditioning.

Cholinergic antagonism impacts selected learning tasks. To understand where scopolamine exerts its action, learning tasks differentially sensitive to hippocampus and amygdala lesions were used. Hippocampal lesions prevent context fear conditioning without effect on tone conditioning. These lesions also produce a time-dependent retrograde deficit in context conditioning. The amygdala is necessary for both tone and context conditioning. To examine the possibility that cholinergic antagonism mimics hippocampal damage or amygdala damage, rats were given scopolamine (1 mg/kg) either before or after fear conditioning. In the fear conditioning procedure, rats received tone-footshock or context-footshock pairings. Evidence of conditioning to the tone and the context was provided by observation of freezing. When given prior to training, scopolamine blocked fear conditioning to the tone in a dose-dependent fashion but had no effect on context conditioning. The impairment of tone conditioning did not occur with methylscopolamine, indicating the central action of the drug. Rats given scopolamine immediately following fear conditioning, tested later in a drug-free state, froze more to the tone than rats given a control injection. The effect of scopolamine on freezing to the context was not reliable. The present results suggest that scopolamine's impact on fear conditioning is mediated by some mechanism other than impaired hippocampal or amygdala functioning.

Acoustic Stimulation↗
PubMed1995

Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo.

Several studies suggest that axonal projections from the hippocampal formation (HF) to the basolateral amygdala (BLA) play a role in Pavlovian fear conditioning to contextual conditional stimuli. We have used electrophysiological techniques to characterize neuronal transmission in these projections in urethane-anesthetized rats. Single-pulse electrical stimulation of the ventral angular bundle (VAB), which carries projections from the HF to the BLA, reliably evoked a biphasic extracellular field potential in the BLA that consisted of an early, negative and a late, positive component. The negative component of the field potential occurred at a short latency (3-8 msec), was both temporally and spatially correlated with VAB-evoked multiple-unit discharges in the BLA, and exhibited properties typical of a monosynaptic response. Infusion of lidocaine or glutamate receptor antagonists into the BLA attenuated VAB-evoked field potentials, indicating that they are generated by local synaptic glutamatergic transmission. Both paired-pulse stimulation and brief trains of high-frequency stimulation (HFS) induced a short-lasting facilitation of BLA field potentials, whereas longer and more numerous trains of HFS produced an enduring, NMDA receptor-dependent long-term potentiation (LTP) of the potentials. The induction of LTP was accompanied by a decrease in paired-pulse facilitation (PPF), suggesting a presynpatic modification underlying its expression. Electrolytic lesions placed in regions of the HF that project to the BLA or excitotoxic lesions placed in the BLA eliminated Pavlovian fear conditioning to a contextual conditional stimulus. The critical role of both structures in context conditioning implicates plasticity at HF-BLA synapses in this form of learning.

Amygdala↗
PubMed1994

Sex differences in hippocampal long-term potentiation (LTP) and Pavlovian fear conditioning in rats: positive correlation between LTP and contextual learning.

Three experiments investigated sex differences in hippocampal long-term potentiation (LTP) and Pavlovian fear conditioning in rats. Experiment 1 revealed a robust sex difference in the magnitude of LTP induced at perforant path synapses in the dentate gyrus of pentobarbital-anesthetized rats. This sex difference in LTP was evident in rats of 35 and 60 days of age and was not the result of pre-LTP sex differences in perforant path synaptic transmission; 20-day-old rats did not show LTP. An analysis of field potentials evoked during LTP induction revealed a sex difference in the magnitude of N-methyl-D-aspartate (NMDA) receptor activation that was highly correlated with the magnitude of LTP. Experiment 2 showed that males condition more fear, measured as freezing, to the contextual conditional stimuli (CSs) of a conditioning chamber compared to their female counterparts. This sex difference in conditional freezing was apparent with both low and high unconditional stimulus (US, footshock) intensities. Experiment 3 revealed that the enhanced fear conditioning in males was specific to contextual CSs, and consisted of a more rapid rate of conditioning. Together, these experiments reveal a positive correlation between the magnitude of hippocampal LTP and a form of learning that depends on the hippocampus. Furthermore, they suggest a neural basis for sex differences in hippocampus-dependent learning tasks.

Acoustic Stimulation↗
PubMed1994

Pavlovian conditioning alters cortical microtubule-associated protein-2.

Three experiments indicate that Pavlovian conditioning to tone alters microtubule-associated protein-2 (MAP-2) in the temporal cortex. First, increased MAP-2 immunohistochemistry was evident in temporal cortex following tone-shock pairings but not light-shock pairings. In the second experiment, animals given tone paired with shock (compared with animals trained with tone unpaired with shock or given tone only) showed MAP-2 immunohistochemical changes in the temporal cortex, as well as in the frontal and cingulate cortex, the hippocampus and amygdala. In experiment 3, quantitative immunoblots showed decreased intact MAP-2 and increased breakdown products selectively in temporal cortex following fear conditioning to tone. Conditioning to tone also increased sizes of MAP-2 rich pyramidal somata and apical dendrites in temporal and frontal cortex.

Acoustic Stimulation↗
PubMed1994

NMDA processes mediate anterograde amnesia of contextual fear conditioning induced by hippocampal damage: immunization against amnesia by context preexposure.

Hippocampal lesions in rats produce both a retrograde and an anterograde amnesia of contextual fear conditioning. The present experiments examined the anterograde deficit in context conditioning. The deficit produced by electrolytic hippocampal lesions was apparent when training occurred on 7, 14, or 28 days following surgery, confirming the durability of the amnesia. The role of the hippocampus in context conditioning may be related to an NMDA (N-methyl-D-aspartate) receptor-mediated process. Both NMDA hippocampal lesions and intrahippocampal administration of an NMDA antagonist produced anterograde amnesia. Animals preexposed to the conditioning context 28 days prior to hippocampal lesioning were protected from the deficit normally produced by the lesions. Thus, the hippocampus must form a contextual representation during preexposure that is subsequently stored elsewhere. Once formed this representation of the context can be associated with an unconditional stimulus.

Animals↗
PubMed1994

Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala.

Rats, with chronic cannula placed bilaterally in the amygdala, received infusions of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) before contextual Pavlovian fear conditioning. Administration of APV to the basolateral nucleus prevented acquisition of fear. Central nucleus infusions had no effect. It is concluded that an NMDA-mediated process near the basolateral region of the amygdala (e.g., lateral or basolateral nucleus) is essential for the learning of fear.

2-Amino-5-phosphonovalerate↗
PubMed1994

Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats.

The influence of water deprivation on hippocampal long-term potentiation (LTP), theta rhythm, and contextual fear conditioning in rats was examined. In Experiment 1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-anesthetized rats. Water deprivation did not affect baseline cell excitability or low-frequency synaptic transmission in the dentate gyrus, but it increased the magnitude of perforant path LTP and elevated the proportion of theta rhythm in the EEG. In Experiment 2, rats were classically conditioned to fear a novel context through the use of aversive footshocks. Water deprivation facilitated the rate of contextual fear conditioning but did not alter the asymptote of learning. Experiment 3 demonstrated that the facilitation of contextual fear conditioning was not due to a change in unconditional shock sensitivity. These results suggest that water deprivation exerts an influence on contextual fear conditioning by modulating hippocampal LTP and theta rhythm and that these processes serve to encode contextual information during learning.

Animals↗
PubMed1994

Differential effects of the N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues.

Intracerebroventricular (icv) administration of the N-methyl-D-aspartate receptor (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) before tone-shock pairings caused a dose-dependent suppression of acquisition of fear of contextual cues associated with shock. Acquisition of fear of the tone was not impaired. Experiment 2 showed that the fear of the tone was associative and that this tone-shock association was less affected by APV than was a context-shock association. Rats receiving APV before context-shock pairings showed an equivalent loss of fear regardless of whether testing occurred 1 or 28 days after training. It appears that icv administration of APV blocks acquisition of context conditioning by affecting NMDA receptors in the hippocampus. Activity at these receptors at the time of acquisition seems critical for later expression of both intermediate (1 day to 2 weeks) and remote (4 weeks) fear memories.

2-Amino-5-phosphonovalerate↗
PubMed1994

Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone conditional stimulus (CS) and an aversive footshock unconditional stimulus (US). Twenty-four and 48 hr following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus.

Animals↗