Biomedical subjects

Denis Paré

Publications and source records attributed to Denis Paré.

At least 19 recordsLinked to original sources

PubMed2006

NMDA-dependent facilitation of corticostriatal plasticity by the amygdala.

Emotions generally improve memory, and the basolateral amygdala (BLA) is believed to mediate this effect. After emotional arousal, BLA neurons increase their firing rate, facilitating memory consolidation in BLA targets. The enhancing effects of BLA activity extend to various types of memories, including motor learning, which is thought to involve activity-dependent plasticity at corticostriatal synapses. However, the underlying mechanisms are unknown. Here we show that the NMDA-to-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) ratio is nearly twice as high at BLA as compared with cortical synapses onto principal striatal neurons and that activation of BLA inputs greatly facilitates long-term potentiation induction at corticostriatal synapses. This facilitation was NMDA-dependent, but it occurred even when BLA and cortical stimuli were 0.5 s apart during long-term potentiation induction. Overall, these results suggest that BLA activity opens long time windows during which the induction of corticostriatal plasticity is facilitated.

Amygdala↗

PubMed2006

Emotional enhancement of memory via amygdala-driven facilitation of rhinal interactions.

Emotions generally facilitate memory, an effect mediated by the basolateral amygdala (BLA). To study the underlying mechanisms, we recorded BLA, perirhinal and entorhinal neurons during an appetitive trace-conditioning task. We focused on the rhinal cortices because they constitute the interface between the hippocampus, a mediator of memory consolidation, and the neocortex, the storage site of declarative memories. We found that, after unexpected rewards, BLA activity increased impulse transmission from perirhinal to entorhinal neurons and that this effect decayed as the association between conditioned stimuli and rewards was learned. At this late phase of learning, the BLA effect occurred when the animals were anticipating the reward. By enhancing the processing of sensory cues, the BLA-mediated facilitation of rhinal interactions may explain how the amygdala promotes memory formation in emotional conditions.

Action Potentials↗

PubMed2006

Ultrastructural organization of medial prefrontal inputs to the rhinal cortices.

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) plays a critical role in the formation, retrieval and long-term storage of hippocampal-dependent memories. Consistent with this, there are direct hippocampal projections to the mPFC. Moreover, the mPFC sends robust projections to the perirhinal and entorhinal cortices, two interconnected cortical fields that funnel information into and out of the hippocampus. However, the significance of the latter projection remains unclear because no data are available regarding the rhinal targets of mPFC axons. This question was examined in the present study using a combination of anterograde tracing with Phaseolus vulgaris leucoagglutinin and pre-embedding gamma-aminobutyric acid (GABA) immunocytochemistry in guinea pigs. Following Phaseolus vulgaris leucoagglutinin injections in the mPFC, anterogradely labeled axons were seen in the perirhinal (mainly superficial layers) and lateral entorhinal (mainly deep layers) cortices. In the electron microscope, the synaptic articulation of anterogradely labeled mPFC axon terminals with perirhinal and entorhinal neurons was found to be nearly identical. In these two rhinal fields, mPFC axon terminals only formed asymmetric synapses, typically with GABA-immunonegative spines ( approximately 70%) but occasionally with dendritic profiles ( approximately 30%), half of which were GABA immunopositive. In the light of earlier observations, these findings indicate that mPFC inputs exert mainly excitatory effects in the rhinal cortices, prevalently on principal neurons. Thus, these results suggest that the mPFC may affect hippocampal-dependent memories by enhancing impulse traffic into and out of the hippocampus at the level of the rhinal cortices.

Animals↗

PubMed2006

Feedforward inhibition regulates perirhinal transmission of neocortical inputs to the entorhinal cortex: ultrastructural study in guinea pigs.

The rhinal cortices constitute the main route for impulse traffic to and from the hippocampus. Tracing studies have revealed that the perirhinal cortex forms strong reciprocal connections with the neo- and entorhinal cortex (EC). However, physiological investigations indicate that perirhinal transmission of neocortical and EC inputs occurs with a low probability. In search of an explanation for these contradictory findings, we have analyzed synaptic connections in this network by combining injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) into the neocortex, area 36, or area 35 with gamma-aminobutyric acid (GABA) immunocytochemistry and electron microscopic observations. Within area 36, neocortical axon terminals formed only asymmetric synapses, usually with GABA-negative spines (87%), and less frequently with GABA-immunopositive (GABA+) dendrites (13%). A similar synaptic distribution was observed within area 35 except that asymmetric synapses onto GABA+ dendrites were more frequent (23% of synapses). Examination of the projections from area 36 to area 35 and from both regions to the EC revealed an even higher incidence of asymmetric synapses onto GABA+ dendrites (35 and 32%, respectively) than what was observed in the neocortical projection to areas 36 and 35. Furthermore, some of the neocortical and perirhinal terminals containing PHAL and GABA immunolabeling formed symmetric synapses onto GABA-negative dendrites in their projection sites (neocortex to area 35, 16%; area 36 to 35, 7%; areas 36-35 to EC, 12%). Taken together, these findings suggest that impulse transmission through the rhinal circuit is subjected to strong inhibitory influences, reconciling anatomical and physiological data about this network.

Animals↗

PubMed2006

Identification of basolateral amygdala projection cells and interneurons using extracellular recordings.

This study tested whether firing rate and spike shape could be used to distinguish projection cells from interneurons in extracellular recordings of basolateral amygdala (BLA) neurons. To this end, we recorded BLA neurons in isoflurane-anesthetized animals with tungsten microelectrodes. Projection cells were identified by antidromic activation from cortical projection sites of the BLA. Although most projection cells fired spontaneously at low rates (<1 Hz), an important subset fired at higher rates (up to 6.8 Hz). In fact, the distribution of firing rates in projection cells and unidentified BLA neurons overlapped extensively, even though the latter cell group presumably contains a higher proportion of interneurons. The only difference between the two distributions was a small subset (5.1%) of unidentified neurons with unusually high firing rates (9-16 Hz). Similarly, distributions of spike durations in both cell groups were indistinguishable, although most of the fast-firing neurons had spike durations at the low end of the distribution. However, we observed that spike durations depended on the exact position of the electrode with respect to the recorded cell, varying by as much as 0.7 ms. Thus neither firing rate nor spike waveform allowed for unequivocal separation of projection cells from interneurons. Nevertheless, we propose the use of two firing rate cutoffs to obtain relatively pure samples of projection cells and interneurons: < or =1 Hz for projection cells and > or =7 Hz for fast-spiking interneurons. Supplemented with spike-duration cutoffs of > or =0.7 ms for projection cells and < or =0.5 ms for interneurons, this approach should keep instances of misclassifications to a minimum.

Action Potentials↗

PubMed2005

Prefrontal control of the amygdala.

Accumulating evidence indicates that phobic and posttraumatic anxiety disorders likely result from a failure to extinguish fear memories. Extinction normally depends on a new learning that competes with the original fear memory and is driven by medial prefrontal cortex (mPFC) projections to the amygdala. Although mPFC stimulation was reported to inhibit the central medial (CEm) amygdala neurons that mediate fear responses via their brainstem and hypothalamic projections, it is unclear how this inhibition is generated. Because the mPFC has very sparse projections to CEm output neurons, the mPFC-evoked inhibition of the CEm is likely indirect. Thus, this study tested whether it resulted from a feedforward inhibition of basolateral amygdala (BLA) neurons that normally relay sensory inputs to the CEm. However, our results indicate that mPFC inputs excite rather than inhibit BLA neurons, implying that the inhibition of CEm cells is mediated by an active gating mechanism downstream of the BLA.

Amygdala↗

PubMed2005

Characterization of synaptic conductances and integrative properties during electrically induced EEG-activated states in neocortical neurons in vivo.

The activation of the electroencephalogram (EEG) is paralleled with an increase in the firing rate of cortical neurons, but little is known concerning the conductance state of their membrane and its impact on their integrative properties. Here, we combined in vivo intracellular recordings with computational models to investigate EEG-activated states induced by stimulation of the brain stem ascending arousal system. Electrical stimulation of the pedonculopontine tegmental (PPT) nucleus produced long-lasting (approximately 20 s) periods of desynchronized EEG activity similar to the EEG of awake animals. Intracellularly, PPT stimulation locked the membrane into a depolarized state, similar to the up-states seen during deep anesthesia. During these EEG-activated states, however, the input resistance was higher than that during up-states. Conductance measurements were performed using different methods, which all indicate that EEG-activated states were associated with a synaptic activity dominated by inhibitory conductances. These results were confirmed by computational models of reconstructed pyramidal neurons constrained by the corresponding intracellular recordings. These models indicate that, during EEG-activated states, neocortical neurons are in a high-conductance state consistent with a stochastic integrative mode. The amplitude and timing of somatic excitatory postsynaptic potentials were nearly independent of the position of the synapses in dendrites, suggesting that EEG-activated states are compatible with coding paradigms involving the precise timing of synaptic events.

Animals↗

PubMed2005

Activity-dependent synaptic plasticity in the central nucleus of the amygdala.

Much evidence indicates that fear conditioning involves potentiation of some thalamic inputs to the lateral amygdala (LA). In turn, the LA would excite more neurons in the central nucleus (CE), leading to the generation of fear responses via their brainstem and hypothalamic projections. However, the posterior thalamus not only projects to LA but also to the medial sector of CE (CEm), suggesting that CEm might also be a site of plasticity. To test whether CEm also exhibits activity-dependent synaptic plasticity, we performed whole-cell recordings of CEm neurons in amygdala slices and stimulated thalamic axons coursing through the internal capsule and, as a control, the basolateral (BL) nucleus. High-frequency stimulation of thalamic inputs led to a long-lasting potentiation of thalamic responses, whereas BL-evoked responses remained unchanged. This thalamic long-term potentiation (LTP) developed even when slices were prepared with a cut severing the connections between the LA and CEm but was greatly reduced when an NMDA receptor antagonist was added to the perfusate shortly before and during LTP induction. Yet, intracellular dialysis with the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate did not prevent induction of the thalamic LTP, suggesting that presynaptic NMDA receptors are required for its induction. Consistent with this, the thalamic LTP also developed when the cells were dialyzed with a calcium chelator or kept hyperpolarized during induction. Finally, this thalamic LTP was associated with reduced amounts of paired-pulse facilitation, suggesting that it is expressed presynaptically. These results are consistent with the idea that the CEm plays an active role in fear conditioning.

2-Amino-5-phosphonovalerate↗

PubMed2005

Interaction between amygdala and neocortical inputs in the perirhinal cortex.

The rhinal cortices play a critical role in high-order perceptual/mnemonic functions and constitute the main route for impulse traffic to and from the hippocampus. However, previous work has revealed that neocortical stimuli that activate a large proportion of perirhinal neurons are unable to discharge entorhinal cells. In search of mechanisms that might facilitate impulse transfer from the neocortex to the entorhinal cortex, we have examined changes in excitability produced by activation of the lateral amygdala (LA) in isoflurane-anesthetized animals. LA stimulation activated a large proportion of peri- and entorhinal neurons. However, conditioning LA stimuli did not increase the ability of neocortical inputs to activate entorhinal cells even though such pairing produced marked increases in neocortically evoked field potentials and orthodromic firing in the perirhinal cortex. Moreover, increased neocortically evoked perirhinal field potentials and unit responses persisted when the conditioning LA shock was replaced by another neocortical stimulus at the same or at a different site as the testing shock. This perirhinal paired-pulse facilitation (PPF) was maximal with interstimulus intervals of approximately 100 ms. Intracellular recordings of perirhinal neurons revealed that the PPF was generally associated with a rapid shift in the balance between inhibition and excitation, leading to an overall increase in perirhinal responsiveness. The significance of these findings for the role of the perirhinal cortex is discussed.

Action Potentials↗

PubMed2005

Synaptic plasticity in the central nucleus of the amygdala.

In recent years, the amygdala has emerged as a critical site of plasticity for the acquisition of various forms of Pavlovian learning, either aversive or appetitive. In most of these models, the critical site of plasticity has been localized to the basolateral complex of the amygdala (BLA). In contrast, the central nucleus of the amygdala has emerged as a passive relay of potentiated BLA outputs toward downstream effectors. At odds with this view, however, recent studies suggest that the central nucleus may also be a site of plasticity and play an active role in some forms of Pavlovian learning. The present review summarizes the evidence supporting this possibility.

Amygdala↗

PubMed2004

Role of amygdala oscillations in the consolidation of emotional memories.

Much evidence indicates that emotional arousal generally improves memory and that the amygdala is responsible for this effect. The available data suggest that stress hormones and neuromodulators released in emotionally arousing conditions alter the activity of basolateral amygdala (BLA) neurons in the hours after the learning episode. In turn, these changes would facilitate synaptic plasticity elsewhere in the brain; however, the biological mechanisms underlying the facilitation of memory consolidation by the BLA remain unknown. This article focuses on data suggesting that synchronized oscillatory BLA activity promotes synaptic plasticity by facilitating interactions between neocortical and temporal lobe areas involved in declarative memory.

Adrenal Cortex Hormones↗

PubMed2004

The rhinal cortices: a wall of inhibition between the neocortex and the hippocampus.

Anatomical data indicate that the parahippocampal region, comprised of the perirhinal (PRC), postrhinal (POR) and entorhinal (ERC) cortices, is an essential link between neocortex and hippocampus. Lesion studies demonstrated that memory functions previously ascribed to the hippocampus depend on the integrity of the rhinal cortices. This review will consider recent data suggesting that the ERC and PRC, far from being passive relay stations, actively gate impulse traffic between neocortex and hippocampus, because they are endowed with a powerful intrinsic inhibitory system. It is proposed that the cross-talk between PRC and ERC is not organized to unrestrictedly transfer information, but to select relevant inputs. The implication of these new evidences for the propagation of epileptiform activity will be considered.

Animals↗

PubMed2004

Presynaptic induction and expression of NMDA-dependent LTP.

It is almost axiomatic in neuroscience that postsynaptically induced NMDA-dependent long-term potentiation (LTP) is a cellular substrate of memory. As a result, memory impairments caused by experimental reductions of NMDA currents are often interpreted as evidence that this form of plasticity is involved in memory formation. However, a recent Nature study indicates that not all NMDA-dependent LTP is induced postsynaptically.

Amygdala↗

PubMed2004

New vistas on amygdala networks in conditioned fear.

It is currently believed that the acquisition of classically conditioned fear involves potentiation of conditioned thalamic inputs in the lateral amygdala (LA). In turn, LA cells would excite more neurons in the central nucleus (CE) that, via their projections to the brain stem and hypothalamus, evoke fear responses. However, LA neurons do not directly contact brain stem-projecting CE neurons. This is problematic because CE projections to the periaqueductal gray and pontine reticular formation are believed to generate conditioned freezing and fear-potentiated startle, respectively. Moreover, like LA, CE may receive direct thalamic inputs communicating information about the conditioned and unconditioned stimuli. Finally, recent evidence suggests that the CE itself may be a critical site of plasticity. This review attempts to reconcile the current model with these observations. We suggest that potentiated LA outputs disinhibit CE projection neurons via GABAergic intercalated neurons, thereby permitting associative plasticity in CE. Thus plasticity in both LA and CE would be necessary for acquisition of conditioned fear. This revised model also accounts for inhibition of conditioned fear after extinction.

Amygdala↗

PubMed2004

Low-probability transmission of neocortical and entorhinal impulses through the perirhinal cortex.

One model of episodic memory posits that during slow-wave sleep (SWS), the synchronized discharges of hippocampal neurons in relation to sharp waves "replay" activity patterns that occurred during the waking state, facilitating synaptic plasticity in the neocortex. Although evidence of replay was found in the hippocampus in relation to sharp waves, it was never shown that this activity reached the neocortex. Instead, it was assumed that the rhinal cortices faithfully transmit information from the hippocampus to the neocortex and reciprocally. Here, we tested this idea using 3 different approaches. 1) Stimulating electrodes were inserted in the entorhinal cortex and temporal neocortex and evoked unit responses were recorded in between them, in the intervening rhinal cortices. In these conditions, impulse transfer occurred with an extremely low probability, in both directions. 2) To rule out the possibility that this unreliable transmission resulted from the artificial nature of electrical stimuli, crosscorrelation analyses of spontaneous neocortical, perirhinal, and entorhinal firing were performed in unanesthetized animals during the states of waking and SWS. Again, little evidence of propagation could be obtained in either state. 3) To test the idea that propagation occurs only when large groups of neurons are activated within a narrow time window, we computed perievent histograms of neocortical, perirhinal, and entorhinal neuronal discharges around large-amplitude sharp waves. However, these synchronized entorhinal discharges also failed to propagate across the perirhinal cortex. These findings suggest that the rhinal cortices are more than a relay between the neocortex and hippocampus, but rather a gate whose properties remain to be identified.

Animals↗

PubMed2003

Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.

In extinction of auditory fear conditioning, rats learn that a tone no longer predicts the occurrence of a footshock. Recent lesion and unit recording studies suggest that the medial prefrontal cortex (mPFC) plays an essential role in the inhibition of conditioned fear following extinction. mPFC has robust projections to the amygdala, a structure that is known to mediate the acquisition and expression of conditioned fear. Fear conditioning potentiates the tone responses of neurons in the basolateral amygdala (BLA), which excite neurons in the central nucleus (Ce) of the amygdala. In turn, the Ce projects to the brainstem and hypothalamic areas that mediate fear responses. The present study was undertaken to test the hypothesis that the mPFC inhibits conditioned fear via feedforward inhibition of Ce output neurons. Recording extracellularly from physiologically identified brainstem-projecting Ce neurons, we tested the effect of mPFC prestimulation on Ce responsiveness to synaptic input. In support of our hypothesis, mPFC prestimulation dramatically reduced the responsiveness of Ce output neurons to inputs from the insular cortex and BLA. Thus, our findings support the idea that mPFC gates impulse transmission from the BLA to Ce, perhaps through GABAergic intercalated cells, thereby gating the expression of conditioned fear.

Action Potentials↗

PubMed2003

Conservation of total synaptic weight through balanced synaptic depression and potentiation.

Memory is believed to depend on activity-dependent changes in the strength of synapses. In part, this view is based on evidence that the efficacy of synapses can be enhanced or depressed depending on the timing of pre- and postsynaptic activity. However, when such plastic synapses are incorporated into neural network models, stability problems may develop because the potentiation or depression of synapses increases the likelihood that they will be further strengthened or weakened. Here we report biological evidence for a homeostatic mechanism that reconciles the apparently opposite requirements of plasticity and stability. We show that, in intercalated neurons of the amygdala, activity-dependent potentiation or depression of particular glutamatergic inputs leads to opposite changes in the strength of inputs ending at other dendritic sites. As a result, little change in total synaptic weight occurs, even though the relative strength of inputs is modified. Furthermore, hetero- but not homosynaptic alterations are blocked by intracellular dialysis of drugs that prevent Ca2+ release from intracellular stores. Thus, in intercalated neurons at least, inverse heterosynaptic plasticity tends to compensate for homosynaptic long-term potentiation and depression, thus stabilizing total synaptic weight.

Amygdala↗

PubMed2003

Feedback inhibition defines transverse processing modules in the lateral amygdala.

The lateral amygdaloid (LA) nucleus is the main input station of the amygdala for sensory afferents. However, it is unclear how the lateral nucleus transforms these inputs, because its intrinsic connectivity is poorly understood. Here, we took advantage of the fact that glutamatergic neurons of the lateral nucleus send a primarily unidirectional projection to the basomedial nucleus. Consequently, it was possible to infer the targets of their intranuclear axons (projection cells vs inhibitory interneurons) by backfiring some projection neurons from the basomedial nucleus and analyzing evoked responses in other LA projection cells. Basomedial stimuli evoked markedly different synaptic responses depending on the orientation of the slices. In coronal slices (intact and decorticated), the prevalent response of LA neurons was an inhibition, regardless of the stimulation intensity. This inhibition was sensitive to GABA(A) and non-NMDA receptor antagonists, suggesting that it was mediated by the activation of GABAergic cells of the LA. In contrast, basomedial stimuli primarily evoked EPSPs in horizontal slices, regardless of the position of recorded neurons. In light of these findings, we conclude that the prevalent target of the intrinsic axon collaterals of projection cells depend on the rostrocaudal position of target neurons with respect to the parent cell body: inhibitory interneurons at rostrocaudal proximity versus other projection cells at a distance. Thus, feedback interneurons effectively divide the lateral nucleus in transverse processing modules that prevent runaway excitation within each module but allow intermixing of sensory information in the rostrocaudal plane.

Action Potentials↗