A cGMP-dependent protein kinase gene, foraging, modifies habituation-like response decrement of the giant fiber escape circuit in Drosophila. (41/799)

The Drosophila giant fiber jump-and-flight escape response is a model for genetic analysis of both the physiology and the plasticity of a sensorimotor behavioral pathway. We previously established the electrically induced giant fiber response in intact tethered flies as a model for habituation, a form of nonassociative learning. Here, we show that the rate of stimulus-dependent response decrement of this neural pathway in a habituation protocol is correlated with PKG (cGMP-Dependent Protein Kinase) activity and foraging behavior. We assayed response decrement for natural and mutant rover and sitter alleles of the foraging (for) gene that encodes a Drosophila PKG. Rover larvae and adults, which have higher PKG activities, travel significantly farther while foraging than sitters with lower PKG activities. Response decrement was most rapid in genotypes previously shown to have low PKG activities and sitter-like foraging behavior. We also found differences in spontaneous recovery (the reversal of response decrement during a rest from stimulation) and a dishabituation-like phenomenon (the reversal of response decrement evoked by a novel stimulus). This electrophysiological study in an intact animal preparation provides one of the first direct demonstrations that PKG can affect plasticity in a simple learning paradigm. It increases our understanding of the complex interplay of factors that can modulate the sensitivity of the giant fiber escape response, and it defines a new adult-stage phenotype of the foraging locus. Finally, these results show that behaviorally relevant neural plasticity in an identified circuit can be influenced by a single-locus genetic polymorphism existing in a natural population of Drosophila.  (+info)

Comparison of odor receptive field plasticity in the rat olfactory bulb and anterior piriform cortex. (42/799)

Recent work in the anterior piriform cortex (aPCX) has demonstrated that cortical odor receptive fields are highly dynamic, showing rapid changes of both firing rate and temporal patterning within relatively few inhalations of an odor, despite relatively maintained, patterned input from olfactory bulb mitral/tufted cells. The present experiment examined the precision (odor-specificity) of this receptive field plasticity and compared it with the primary cortical afferent, olfactory bulb mitral/tufted cells. Adult Long-Evans hooded rats, urethan anesthetized and freely breathing, were used for single-unit recording from mitral/tufted and aPCX layer II/III neurons. Partial mapping of receptive fields to alkane odors (pentane, heptane, and nonane) was performed before and immediately after habituation (50-s exposure) to one of the alkanes. The results demonstrated that odor habituation of aPCX responses was odor specific, with minimal cross-habituation between alkanes differing by as few as two carbons. Mitral/tufted cells, however, showed strong cross-habituation within the odor set with the most profound cross effects to carbon chains shorter than the habituating stimulus. The results suggest that although mitral/tufted cells and aPCX neurons have roughly similar odor receptive fields, aPCX neurons have significantly better odor discrimination within their receptive field. The results have important implications for understanding the underlying bases of receptive fields in olfactory system neurons and the mechanisms of odor discrimination and memory.  (+info)

Non-associative learning and serotonin induce similar bi-directional changes in excitability of a neuron critical for learning in the medicinal leech. (43/799)

In studies of the cellular basis of learning, much attention has focused on plasticity in synaptic transmission in terms of transmitter release and the number or responsiveness of neurotransmitter receptors. However, changes in postsynaptic excitability independent of receptors may also play an important role. Changes in excitability of a single interneuron in the leech, the S-cell, were measured during non-associative learning of the whole-body shortening reflex. This interneuron was chosen because it is known to be necessary for sensitization and full dishabituation of the shortening response. During sensitization, S-cell excitability increased, and this enhancement corresponded to facilitation of the shortening reflex and increased S-cell activity during the elicited response. During habituation training, there was a decrement in both the shortening reflex and the elicited S-cell activity, along with decreased S-cell excitability. Conversely, dishabituation facilitated both the shortening response and S-cell activity during shortening, with an accompanying increase in S-cell excitability. Bath application of 1-10 micrometer serotonin (5HT), a modulatory neurotransmitter that is critical for sensitization, for full dishabituation, and for associative learning, increased S-cell excitability. S-cell excitability also increased after stimulation of the serotonergic Retzius cells. However, focal application of serotonin onto the S-cell soma hyperpolarized the interneuron, and bath application of a lower dose of serotonin (0.1 micrometer) decreased excitability. The observed changes in postsynaptic excitability appear to contribute to non-associative learning, and modulatory neurotransmitters, such as serotonin, evidently help regulate excitability. Such changes in S-cell excitability may also be relevant for more complex, associative forms of learning.  (+info)

Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. (44/799)

Prepulse inhibition (PPI) of the acoustic startle response is an operational measure of sensorimotor gating that can be assessed in animals and in humans. Serotonin releasers such as MDMA disrupt PPI and reduce startle habituation in rodents. These effects are prevented by pretreatment with selective serotonin uptake inhibitors, indicating that the effect of MDMA on startle plasticity is largely due to carrier-mediated release of serotonin from presynaptic terminals. In contrast, MDMA has been shown to increase PPI in humans. It is unclear, however, whether the MDMA-induced increase in PPI in humans is also dependent on carrier-mediated serotonin release and which postsynaptic receptors are involved. We investigated the effects of three different pretreatments on the MDMA-induced effects on PPI and habituation in humans. Pretreatments were: (1) the highly selective serotonin uptake inhibitor citalopram (40 mg IV) in 16 subjects, (2) the D(2) antagonist haloperidol (1.4 mg IV) in 14 subjects, and (3) the 5-HT(2A/C) antagonist ketanserin (50 mg PO) in 14 subjects. Each of the three studies used a double-blind placebo-controlled design. All healthy volunteers were examined four times at 2-4-week intervals after placebo, pretreatment, MDMA (1.5 mg/kg PO), and pretreatment plus MDMA. MDMA increased PPI. Habituation was not altered by MDMA, although MDMA-induced individual differences on habituation and psychological symptoms were inversely correlated. Citalopram attenuated the MDMA-induced increase in PPI and most of the psychological effects of MDMA. Neither haloperidol nor ketanserin had any effect on PPI increases produced by MDMA, although each partially attenuated some MDMA-induced psychological effects. Results are consistent with the view that MDMA increases PPI of the acoustic startle reflex in humans via release of presynaptic serotonin.  (+info)

Pharmacological differences between memory consolidation of habituation to an open field and inhibitory avoidance learning. (45/799)

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-microl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), of the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5), of the protein kinase A inhibitor Rp-cAMPs (0.5 microg/side), of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks.  (+info)

Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance. (46/799)

Regional cerebral blood flow (BF) was examined in regions of the medial prefrontal cortex (MPFC) with positron-emission tomography while subjects performed two cognitive tasks, reading nouns aloud and generating appropriate verbs for the same nouns. The control task was passive viewing of the same words. BF was reduced in regions of the MPFC during word reading and naive verb generation, relative to a control state in which the subjects passively viewed nouns. Practicing verb generation produced improved performance, as measured by response time, which was strongly correlated with further reductions in MPFC and hypothalamic BF. After practice, when verb generation was performed on a novel list of words, reaction times slowed and the pattern of MPFC BF reverted to that seen in the word reading and naive conditions. A separate behavioral study of the verb-generation task indicated that anxiety, high during naive use-generation as measured by heart rate and self-report, decreased with practice on the task but returned with the introduction of a novel list of words. Taken together, these results suggest that the MPFC is part of a network, including the hypothalamus and brainstem, whose activity reflects a dynamic interplay between cognitive task performance and emotion.  (+info)

Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. (47/799)

Regional cerebral blood flow (BF) was examined in the human medial prefrontal cortex (MPFC) with positron emission tomography during anticipatory anxiety. Transient anxiety was induced in normal subjects by having them anticipate a painful shock to the fingers of one hand. BF was decreased during anticipatory anxiety, relative to an eyes-closed resting condition, in two regions of the MPFC (Brodmann Areas 10/32 and 24/25). BF decreases in these areas were inversely correlated with anxiety self rating, such that the least anxious subjects exhibited the largest BF reductions, whereas the most anxious subjects showed no significant BF reduction or a slight increase. BF changes in MPFC and in the midbrain were correlated with each other and with anxiety self rating. These results are consistent with the hypothesis that BF reductions in MPFC, previously observed in cognitive tasks, reflect a dynamic balance between focused attention and subject anxiety and may occur from a functionally active baseline or default state. The characterization of such relationships within the human brain enables new insights into the integration of cognition and emotion.  (+info)

Criticisms of the satiety hypothesis as an explanation for within-session decreases in responding. (48/799)

The authors of four papers recently reported that satiation provides a better explanation than habituation for within-session decreases in conditioned responding. Several arguments question this conclusion. First, the contribution of habituation to within-session changes in responding seems clearly established. Information that is consistent with habituation, but that is difficult to reconcile with satiation, is not adequately addressed. Second, the limited evidence offered in support of satiation is ambiguous because the results are just as compatible with habituation as with other satiety variables. Finally, the term satiation is used in an intuitive way that is sometimes contradicted by research about the termination of ingestion. Use of the technical term satiation in a way that differs from its conventional usage will only isolate operant psychology from other areas of psychological research.  (+info)