Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation

A long-standing hypothesis termed “Hebbian plasticity” suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control

Pavlovian aversive conditioning requires learning of the association between a conditioned stimulus (CS) and an unconditioned, aversive stimulus (US) but also involves encoding the time interval between the two stimuli. The neurobiological bases of this time interval learning are unknown. Here, we show that in rats, the dorsal striatum and basal amygdala belong to a common functional network underlying temporal expectancy and learning of a CS–US interval. Importantly, changes in coherence between striatum and amygdala local field potentials (LFPs) were found to couple these structures during interval estimation within the lower range of the theta rhythm (3–6 Hz). Strikingly, we also show that a change to the CS–US time interval results in long-term changes in cortico-striatal synaptic efficacy under the control of the amygdala. Collectively, this study reveals physiological correlates of plasticity mechanisms of interval timing that take place in the striatum and are regulated by the amygdala

Scientific opinion on dietary reference values for thiamin

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derived dietary reference values (DRVs) for thiamin (vitamin B1). The Panel considers that data from depletion\u2013repletion studies in adults on the amount of dietary thiamin intake associated with the erythrocyte transketolase activity coefficient (\u3b1ETK) < 1.15, generally considered to reflect an adequate thiamin status, or with the restoration of normal (baseline) erythrocyte transketolase activity, without a sharp increase in urinary thiamin excretion, can be used to estimate thiamin requirement. In the absence of new scientific evidence, the Panel endorses the average requirement (AR) of 0.072 mg/MJ (0.3 mg/1,000 kcal) for all adults proposed by the Scientific Committee for Food (SCF) in 1993 on the basis of one depletion\u2013repletion study, in which both \u3b1ETK and urinary thiamin excretion were measured. Results from other depletion\u2013repletion studies are in agreement with this value. The Panel agrees on the coefficient of variation of 20% used by the SCF to cover uncertainties related to distribution of thiamin requirements in the general population, and endorses the population reference intake (PRI) of 0.1 mg/MJ (0.4 mg/1,000 kcal) set by the SCF for all adults. The same AR and PRI as for adults, expressed in mg/MJ, are proposed for infants aged 7\u201311 months, children aged 1 to < 18 years, and during pregnancy and lactation, under the assumption that the relationship between thiamin requirement and energy requirement is the same in all population groups

Beyond Freezing: Temporal Expectancy of an Aversive Event Engages the Amygdalo–Prefronto–Dorsostriatal Network

International audienceDuring Pavlovian aversive conditioning, a neutral conditioned stimulus (CS) becomes predictive of the time of arrival of an aversive unconditioned stimulus (US). Using a paradigm where animals had to discriminate between a CS+ (associated with a footshock) and a CS- (never associated with a footshock), we show that, early in training, dynamics of neuronal oscillations in an amygdalo-prefronto-striatal network are modified during the CS+ in a manner related to the CS-US time interval (30 or 10 s). This is the case despite a generalized high level of freezing to both CS+ and CS-. The local field potential oscillatory power was decreased between 12 and 30 Hz in the dorsomedial striatum (DMS) and increased between 55 and 95 Hz in the prelimbic cortex (PL), while the coherence between DMS, PL, and the basolateral amygdala was increased in the 3-6 Hz frequency range up to the expected time of US arrival only for the CS+ and not for the CS-. Changing the CS-US interval from 30 to 10 s shifted these changes in activity toward the newly learned duration. The results suggest a functional role of the amygdalo-prefronto-dorsostriatal network in encoding temporal information of Pavlovian associations independently of the behavioral output

Detection of temporal error triggers reconsolidation of amygdala-dependent memories.

International audienceUpdating memories is critical for adaptive behaviors, but the rules and mechanisms governing that process are still not well defined. During a limited time window, the reactivation of consolidated aversive memories triggers memory lability and induces a plasticity-dependent reconsolidation process in the lateral nucleus of amygdala (LA) [1-5]. However, whether new information is necessary for initiating reconsolidation is not known. Here we show that changing the temporal relationship between the conditioned stimulus (CS) and unconditioned stimulus (US) during reactivation is sufficient to trigger synaptic plasticity and reconsolidation of an aversive memory in the LA. These findings demonstrate that time is a core part of the CS-US association and that new information must be presented during reactivation in order to trigger LA-dependent reconsolidation processes. In sum, this study provides new basic knowledge about the precise rules governing memory reconsolidation of aversive memories that might be used to treat traumatic memories

Updating of aversive memories after temporal error detection is differentially modulated by mTOR across development.

International audienceThe updating of a memory is triggered whenever it is reactivated and a mismatch from what is expected (i.e., prediction error) is detected, a process that can be unraveled through the memory's sensitivity to protein synthesis inhibitors (i.e., reconsolidation). As noted in previous studies, in Pavlovian threat/aversive conditioning in adult rats, prediction error detection and its associated protein synthesis-dependent reconsolidation can be triggered by reactivating the memory with the conditioned stimulus (CS), but without the unconditioned stimulus (US), or by presenting a CS-US pairing with a different CS-US interval than during the initial learning. Whether similar mechanisms underlie memory updating in the young is not known. Using similar paradigms with rapamycin (an mTORC1 inhibitor), we show that preweaning rats (PN18-20) do form a long-term memory of the CS-US interval, and detect a 10-sec versus 30-sec temporal prediction error. However, the resulting updating/reconsolidation processes become adult-like after adolescence (PN30-40). Our results thus show that while temporal prediction error detection exists in preweaning rats, specific infant-type mechanisms are at play for associative learning and memory