Induction of activity-dependent LTD requires muscarinic receptor activation in medial prefrontal cortex

The medial prefrontal cortex (mPFC) forms part of a neural circuit involved in the formation of lasting associations between objects and places. Cholinergic inputs from the basal forebrain innervate the mPFC and may modulate synaptic processes required for the formation of object-in-place memories. To investigate whether acetylcholine regulates synaptic function in the rat mPFC, whole-cell voltage-clamp recordings were made from pyramidal neurons in layer V. Bath application of the cholinergic agonist carbachol caused a potent and long-term depression (LTD) of synaptic responses that was blocked by the muscarinic receptor antagonist scopolamine and was mimicked, in part, by the M 1 receptor agonists McN-A-343 or AF102B. Furthermore, inhibition of PKC blocked carbachol-mediated LTD. We next determined the requirements for activity-dependent LTD in the prefrontal cortex. Synaptic stimulation that was subthreshold for producing LTD did, however, result in LTD when acetylcholine levels were enhanced by inhibition of acetylcholinesterase or when delivered in the presence of the M 1-selective positive allosteric modulator BQCA. Increasing the levels of synaptic stimulation resulted in M 1 receptor-dependent LTD without the need for pharmacological manipulation of acetylcholine levels. These results show that synaptic stimulation of muscarinic receptors alone can be critical for plastic changes in excitatory synaptic transmission in the mPFC. In turn, these muscarinic mediated events may be important in the formation of object-in-place memories. A loss of basal forebrain cholinergic neurons is a classic hallmark of Alzheimer's dementia and our results provide a potential explanation for the loss of memory associated with the disease

Perirhinal cortex lesions impair tests of object recognition memory but spare novelty detection

This article is protected by copyright. All rights reserved. Acknowledgements This work was supported by the Wellcome Trust (WT103722/Z/14/Z). The authors wish to thank L. Kinnavane and J. M. Pearce for their contributions to the manuscript. The authors confirm that they have no known conflicts of interest.Peer reviewedPublisher PD

Fornix lesions can facilitate acquisition of the transverse patterning task: a challenge for configural theories of hippocampal function.

Configural theories of hippocampal function predict that hippocampal dysfunction should impair acquisition of the transverse patterning task, which involves the concurrent solution of three discrimination problems: A+ versus B-; B+ versus C-; and C+ versus A-. The present study tested this prediction in rats using computer-graphic stimuli presented on a touchscreen. Experiment 1 assessed the effects of fornix lesions when the three problems were introduced sequentially (phase 1: A+ vs B-; phase 2: A+ vs B-, B+ vs C-; phase 3: A+ vs B-, B+ vs C-, C+ vs A-). Fornix lesions significantly facilitated acquisition of the complete transverse patterning task (phase 3) but had no effect on the number of sessions or errors required to attain criterion during phase 1 or phase 2. In experiment 2, in which all three problems were presented concurrently from the outset of training, fornix-lesioned animals outperformed control animals during the seventh block of acquisition trials and were not impaired during any stage of acquisition. Importantly, these same animals were significantly impaired on two allocentric spatial tasks: T-maze alternation (experiments 1 and 2) and the Morris Swim Task (experiment 1). These results contradict the predictions of configural theories of hippocampal function and cast doubt on the popular notion that spatial learning is a special case of configural learning

Contrasting roles for DNA methyltransferases and histone deacetylases in single-item and associative recognition memory

Recognition memory enables us to judge whether we have encountered a stimulus before and to recall associated information, including where the stimulus was encountered. The perirhinal cortex (PRh) is required for judgment of stimulus familiarity, while hippocampus (HPC) and medial prefrontal cortex (mPFC) are additionally involved when spatial information associated with a stimulus needs to be remembered. While gene expression is known to be essential for the consolidation of long-term recognition memory, the underlying regulatory mechanisms are not fully understood. Here we investigated the roles of two epigenetic mechanisms, DNA methylation and histone deacetylation, in recognition memory. Infusion of DNA methyltransferase inhibitors into PRh impaired performance in novel object recognition and object-in-place tasks while infusions into HPC or mPFC impaired object-in-place performance only. In contrast, inhibition of histone deacetylases in PRh, but not mPFC, enhanced recognition memory. These results support the emerging role of epigenetic processes in learning and memory

Nicotinic Acetylcholine Receptors Control Encoding and Retrieval of Associative Recognition Memory through Plasticity in the Medial Prefrontal Cortex

Summary: Nicotinic acetylcholine receptors (nAChRs) expressed in the medial prefrontal cortex have critical roles in cognitive function. However, whether nAChRs are required for associative recognition memory and the mechanisms by which nAChRs may contribute to mnemonic processing are not known. We demonstrate that nAChRs in the prefrontal cortex exhibit subtype-specific roles in associative memory encoding and retrieval. We present evidence that these separate roles of nAChRs may rely on bidirectional modulation of plasticity at synaptic inputs to the prefrontal cortex that are essential for associative recognition memory. : Sabec et al. reveal a divergence in function of prefrontal nicotinic receptor subtypes in different stages of long-term associative recognition memory that relates to bidirectional modulation of synaptic plasticity at hippocampal-prefrontal synapses. Keywords: acetylcholine, nicotinic receptor, medial prefrontal cortex, associative recognition memory, plasticit

Työ- ja toimintakyvyssä tapahtuvat subjektiiviset muutokset kuntouttavan työtoiminnan aikana : - tarkastelun kohteena Luonnollisesti töissä -hanke

Tämän opinnäytetyön tavoitteena oli tutkia kuntouttavan työtoiminnan aikana tapahtuneita subjektiivisia muutoksia asiakkaan työ- ja toimintakyvyssä, kun sitä toteutetaan Green Care-menetelmällä. Tutkimuksessa tutkin työ- ja toimintakyvystä hyvinvoinnin, osallisuuden, mielen ja taitojen -osa-alueita. Opinnäytetyöni tilaajana toimi Satakunnan alueella toimiva Luonnollisesti töissä -hanke. Opinnäytetyöni seurantatutkimuksen toteutin kuntouttavan työtoiminnan asiakkaille Kykyviisari 2.0 -kyselyllä, jonka on kehittänyt Työterveyslaitoksen Solmu- ESR -koordinaatiohanke. Seurantatutkimuksen alkukyselyt toteutettiin helmikuussa 2017 ja loppukyselyt toukokuussa 2017. Tutkimuksen kohderyhmänä oli kuusitoista kuntouttavan työtoiminnan asiakasta. Asiakkaista vain kahdeksan vastasi tutkimuksen loppukyselyyn, joten otantana tutkimuksessa oli kahdeksan henkilöä. Kohderyhmän kokemuksien pohjalta voidaan sanoa, että kuntouttava työtoiminta Green Care-menetelmällä toteutettuna kohentaa asiakkaan hyvinvointia, osallisuutta ja mieltä. Tulos on kuitenkin vain suuntaa antava, sillä saadut tutkimustulokset ovat jokaisen yksilöllisiä kokemuksia omasta työ- ja toimintakyvystä.The target of this thesis was to examine the subjective changes in client’s ability to work and function while participating in rehabilitative work when it is carried out with Green Care-method. In the study I examined the sections of welfare, participation, mind and skills. The orderer of this thesis was Luonnollisesti töissä -project operating in Satakunta. I carried out the follow-up study of this thesis for the clients of rehabilitative work with the Kykyviisari 2.0. -survey developed by The Finnish Institute of Occupational Health’s Solmu-ESR-coordination project. The beginning survey of the follow-up study was carried out in February 2017 and the ending survey in May 2017. The target group of the study formed of sixteen clients of rehabilitative work. Only eight of the clients took part in the ending survey and therefore the sampling of the study was eight individuals. According to the experiences of the target group we can say that rehabilitative work carried out with Green Care -method improves the client’s welfare, participation and state of mind. Nevertheless, the results are only approximate because they are one’s own subjective experiences of his ability to work and function

Nicotinic Acetylcholine Receptors Control Encoding and Retrieval of Associative Recognition Memory through Plasticity in the Medial Prefrontal Cortex

International audienceNicotinic acetylcholine receptors (nAChRs) expressed in the medial prefrontal cortex have critical roles in cognitive function. However, whether nAChRs are required for associative recognition memory and the mechanisms by which nAChRs may contribute to mnemonic processing are not known. We demonstrate that nAChRs in the prefrontal cortex exhibit subtype-specific roles in associative memory encoding and retrieval. We present evidence that these separate roles of nAChRs may rely on bidirectional modulation of plasticity at synaptic inputs to the prefrontal cortex that are essential for associative recognition memory