Opioid antagonism impairs acquisition of forebrain-dependent trace-associative learning: An eyeblink conditioning analysis

2014 ◽  
Vol 118 ◽  
pp. 46-50 ◽  
Author(s):  
Ryan M. Loh ◽  
Roberto Galvez
PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95317 ◽  
Author(s):  
Lily S. Chau ◽  
Alesia V. Prakapenka ◽  
Liridon Zendeli ◽  
Ashley S. Davis ◽  
Roberto Galvez

2020 ◽  
Author(s):  
Katarzyna Kita ◽  
Catarina Albergaria ◽  
Ana S. Machado ◽  
Megan R. Carey ◽  
Martin Müller ◽  
...  

AbstractAMPA receptors (AMPARs) mediate excitatory neurotransmission in the CNS and their subunit composition determines synaptic efficacy. Whereas AMPAR subunits GluA1–GluA3 have been linked to particular forms of synaptic plasticity and learning, the functional role of GluA4 remains elusive. Here we used electrophysiological, computational and behavioral approaches to demonstrate a crucial function of GluA4 for synaptic excitation and associative memory formation in the cerebellum. Notably, GluA4-knockout mice had ∼80% reduced mossy fiber to granule cell synaptic transmission. The fidelity of granule cell spike output was markedly decreased despite attenuated tonic inhibition and increased NMDA receptor-mediated transmission. Computational modeling revealed that GluA4 facilitates pattern separation that is important for associative learning. On a behavioral level, while locomotor coordination was generally spared, GluA4-knockout mice failed to form associative memories during delay eyeblink conditioning. These results demonstrate an essential role for GluA4-containing AMPARs in cerebellar information processing and associative learning.


2021 ◽  
Author(s):  
Amy P Rapp ◽  
Timothy J Hark ◽  
John M Power ◽  
M Matthew Oh ◽  
Jeffrey N Savas ◽  
...  

Neuroscience techniques, including in vivo recording, have allowed for a great expansion in knowledge; however, this technology may also affect the very phenomena researchers set out to investigate. Including both female and male mice in our associative learning experiments shed light on sex differences on the impact of chronic implantation of tetrodes on learning. While previous research showed intact female mice acquired trace eyeblink conditioning faster than male and ovariectomized females, implantation of chronic microdrive arrays showed sexually dimorphic effects on learning. Microdrive implanted male mice acquired the associative learning paradigm faster than both intact and ovariectomized females. These effects were not due to the weight of the drive alone, as there were no significant sex-differences in learning of animals that received dummy drive implants without tetrodes lowered into the brain. Tandem mass tag mass spectrometry and western blot analysis suggest that significant alterations in the MAPK pathway, acute inflammation, and brain derived neurotrophic factor may underlie these observed sex- and surgery-dependent effects on learning.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Katarzyna Kita ◽  
Catarina Albergaria ◽  
Ana S Machado ◽  
Megan R Carey ◽  
Martin Mueller ◽  
...  

AMPA receptors (AMPARs) mediate excitatory neurotransmission in the CNS and their subunit composition determines synaptic efficacy. Whereas AMPAR subunits GluA1–GluA3 have been linked to particular forms of synaptic plasticity and learning, the functional role of GluA4 remains elusive. Here we demonstrate a crucial function of GluA4 for synaptic excitation and associative memory formation in the cerebellum. Notably, GluA4-knockout mice had ~80% reduced mossy fiber to granule cell synaptic transmission. The fidelity of granule cell spike output was markedly decreased despite attenuated tonic inhibition and increased NMDA receptor-mediated transmission. Computational network modeling incorporating these changes revealed that deletion of GluA4 impairs granule cell expansion coding, which is important for pattern separation and associative learning. On a behavioral level, while locomotor coordination was generally spared, GluA4-knockout mice failed to form associative memories during delay eyeblink conditioning. These results demonstrate an essential role for GluA4-containing AMPARs in cerebellar information processing and associative learning.


2010 ◽  
Vol 104 (1) ◽  
pp. 346-365 ◽  
Author(s):  
Elena Porras-García ◽  
Raudel Sánchez-Campusano ◽  
David Martínez-Vargas ◽  
Eduardo Domínguez-del-Toro ◽  
Jan Cendelín ◽  
...  

Young adult heterozygous Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance—including the acquisition of new motor abilities—because of the early postnatal degeneration of almost all of their Purkinje and granular cells. Wild-type and Lurcher mice were classically conditioned for eyelid responses using a delay paradigm with or without an electrolytic lesion in the interpositus nucleus. Although the late component of electrically evoked blink reflexes was smaller in amplitude and had a longer latency in Lurcher mice than that in controls, the two groups of animals presented similar acquisition curves for eyeblink conditioning. The lesion of the interpositus nucleus affected both groups of animals equally for the generation of reflex and conditioned eyelid responses. Furthermore, we recorded the multiunitary activity at the red and interpositus nuclei during the same type of associative learning. In both nuclei, the neural firing activity lagged the beginning of the conditioned response (determined by orbicularis oculi muscle response). Although red nucleus neurons and muscle activities presented a clear functional coupling (strong correlation and low asymmetry) across conditioning, the coupling between interpositus neurons and either red nucleus neurons or muscle activities was slightly significant (weak correlation and high asymmetry). Lurcher mice presented a nonlinear coupling (high asymmetry) between red nucleus neurons and muscle activities, with an evident compensatory adjustment in the correlation of firing between interpositus and red nuclei neurons (a coupling with low asymmetry), aimed probably at compensating the absence of cerebellar cortical neurons.


2011 ◽  
Vol 125 (5) ◽  
pp. 687-698 ◽  
Author(s):  
Amanda R. Bolbecker ◽  
Adam B. Steinmetz ◽  
Crystal S. Mehta ◽  
Jennifer K. Forsyth ◽  
Mallory J. Klaunig ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document