Physiology of Learning and Memory

All organisms continuously have to adapt their behavior according to changes in the environment in order to survive. This is particularly important when learning to predict threatening or dangerous situations. Such experience-driven adaptations in behavior are mediated by modifications in brain circuits. We are interested in how brain function changes during learning and memory processes. We focus on classical (Pavlovian) fear conditioning and extinction of fear in mice, a powerful model to study neural mechanisms of associative learning and memory formation.

Our goal is to identify and study molecular, synaptic and cellular substrates of neural circuits in a brain region called the amygdala and fear-related areas that underlie fear and extinction memory. Towards this end, we combine a range of techniques including ex-vivo slice electrophysiology (patch-clamp), imaging, molecular biology, viral gene transfer in vivo and optogenetics, as well as behavioral analysis.

Studying fear and extinction memory not only is an excellent model to understand general principles of memory formation in the brain, but also will provide leads on nervous system dysfunction during inappropriate control of fear behavior in conditions such as human anxiety disorders.    

Research projects
Members
Partners & Collaborations
Publications

The amygdala, a brain structure in the temporal lobe, is a key structure for storing fear memories. Fear memories can be modified by a second learning process called extinction, which is the basis for behavioral therapies in the treatment of anxiety disorders. Here, the individual learns that certain stimuli are not fearful anymore in a specific setting. Extinction depends on a larger brain network comprising the amygdala, the hippocampus and the medial prefrontal cortex, as well as interactions between them. To date, some of the strongest links between neural plasticity and behavioral learning come from studies of fear memory in the amygdala. Changes can be detected ex vivo in recordings from brain slices obtained from trained animals. Our research hinges on using this approach. While plastic changes of sensory inputs to excitatory cells in the amygdala are well understood, inputs from other structures and intra-amygdala inhibitory elements may also undergo plasticity. Our goal is to identify and investigate novel changes in these networks.

One line of research aims to understand properties and function of a specialized group of inhibitory neurons in the amygdala, the intercalated cells. These cells have recently received much attention, as they become activated during fear behaviors and are critical for extinction. However, little is known about their properties and connectivity. We combine electrophysiological, optogenetic and anatomical techniques with behavioural manipulations to understand how they are integrated and process information within amygdala networks and may participate in shaping acquired fear behavior.

A second line of research investigates extinction mechanisms. On the one hand, we are interested in understanding the interactions of amygdala, hippocampus, and prefrontal cortex at the cellular level, which are critical for understanding extinction mechanisms. Towards this end, we use tracing, reporter mice and ex-vivo optogenetic approaches that allow for targeted stimulation of long-range inputs to specific cells in the amygdala. On the other hand, we are interested in processes that modulate consolidation of extinction memory and influence these circuits. In that respect, we explore the idea that sleep, which has been show to be beneficial for many forms of memory, also supports fear extinction.

A third line of research addresses developmental processes in amygdala circuits that could underlie developmental differences in learning behavior. The ability to learn fear first emerges in infancy and changes into adulthood. Extinction learning emerges in juveniles, but is different from adults. We are currently using electrophysiological approaches investigating developmental changes particularly in amygdala inhibitory mechanisms that occur between infancy and adulthood. Furthermore, we are interested in applying molecular manipulations to understand the function of specific inhibitory synapses in amygdala plasticity and learning.


 
Name
Department
Phone
Email
 Ayla Aksoy-Aksel
Ayla Aksoy-Aksel Postdoc
Physiology of Learning and Memory
07071 29-88858 
 Charalampos Brakatselos
Charalampos Brakatselos Internship/Master Student
Physiology of Learning and Memory
89226 
Dr. Ingrid Ehrlich
Dr. Ingrid Ehrlich Research Group Leader
Physiology of Learning and Memory
07071 29-89189 
 Andrea Gall
Andrea Gall
Physiology of Learning and Memory
07071 29-89226 
 Melina Matthiesen
Melina Matthiesen PhD Student
Physiology of Learning and Memory
88858 
 Irene Melo-de-Carvalho
Irene Melo-de-Carvalho
Physiology of Learning and Memory
07071 29-89226 
 Tamara Vasilkovska
Tamara Vasilkovska Masters Student
Physiology of Learning and Memory
07071 29-89226 

SFB 654 (Born lab, Tübingen; Büchel Lab, UKE Hamburg)

Ferraguti Lab (Medical University Innsbruck)

Volkmer Lab (NMI Reutlingen)

 

 

Original Publications

Zussy C, Gómez-Santacana X, Rovira X, De Bundel D, Ferrazzo S, Bosch D, Asede D, Malhaire F, Acher F, Giraldo J, Valjent E, Ehrlich I, Ferraguti F, Pin J-P, Llebaria A, Goudet C. (2017) Dynamic modulation of inflammatory pain-related behaviors by optical control of amygdala metabotropic glutamate receptor 4. Molecular Psychiatry doi: 10.1038/mp.2016.223. [Epub ahead of print]

Saha R, Knapp S, Chakraborty D, Horovitz O, Albrecht A, Kriebel M, Kaphzan H, Ehrlich I, Volkmer H, Richter-Levin G. (2017) GABAergic synapses at the axon initial segment of basolateral amygdala projection neurons modulate fear extinction. Neuropsychopharmacology 42: 473-484.

Melo I and Ehrlich I. (2016) Sleep supports cued fear extinction memory consolidation independent of circadian phase. Neurobiol Learn Mem 132: 9-17

Schönherr S, Seewald A, Kasugai Y, Bosch D, Ehrlich I, and Ferraguti F. (2016) Combined optogenetic and freeze-fracture replica immunolabeling to examine input-specific arrangement of glutamate receptors in mouse amygdala. J Vis Exp 110: e53853

Bosch D, Asede D, and Ehrlich I. (2016) Ex vivo optogenetic dissection of fear circuits in brain slices. J Vis Exp 110: e53628.

Bosch D, and Ehrlich I. (2015) Postnatal maturation of GABAergic modulation of sensory inputs onto lateral amygdala principal neurons. J Physiol 593: 4387-4409.

Asede D, Bosch D, Lüthi A, Ferraguti F, and Ehrlich I. (2015) Sensory inputs to intercalated cells provide fear-learning modulated inhibition to the basolateral amygdala. Neuron 86: 541-554.

Hübner C, Bosch D, Gall A, Lüthi A, and Ehrlich I (2014) Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory. Front Behav Neurosci 8: 64. doi 10.33389/fnbeh.2014.00064

Wolff SBE, Gründemann J, Tovote, P, Krabbe, S, Jacobson, GA, Müller C, Herry C, Ehrlich I, Friedrich RW, Letzkus JJ, and Lüthi A (2014) Amygdala interneuron subtypes control fear learning through disinhibition. Nature 509: 453-458.

Senn V, Wolff SBE., Herry C, Grenier F, Ehrlich I, Gründemann J, Fadok J, Müller C, Letzkus JJ and Lüthi A (2014) Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 81: 428-443.

Ciocchi S, Herry C, Grenier F, Wolff SB, Letzkus JJ, Vlachos I, Ehrlich I, Sprengel R, Deisseroth K, Stadler MB, Müller C, and Lüthi A (2010) Encoding of conditioned fear in central amygdala circuits. Nature 468: 277-282.

Tang W, Ehrlich I, Wolff SBE, Michalski A-M, Wölfl S, Hasan M, Lüthi A, Sprengel R (2009) Faithful expression of multiple proteins via 2A-peptide self-processing: a versatile and reliable method for manipulating brain circuits. J Neurosci 27: 8621-9.

Elkobi A, Ehrlich I, Belelovsky K, Barki-Harrington L, and Rosenblum K (2008) ERK-dependent PSD-95 induction in the gustatory cortex is necessary for taste learning, but not retrieval. Nat Neurosci 11:1149-1151.

Ehrlich I, Klein M, Rumpel S and Malinow R (2007) PSD-95 is required for activity-driven synapse stabilization. Proc Natl Acad Sci USA 104:4176-4181.

Ehrlich I and Malinow R (2004) Postsynaptic density 95 controls AMPA-receptor incorporation during Long-Term Potentiation and experience-driven synaptic plasticity. J Neurosci 24:916-927.

Reviews

Herry C, Ferraguti F, Singewald N, Letzkus JJ, Ehrlich I, and Lüthi A (2010) Neuronal circuits of fear extinction. Eur J Neurosci 31: 599-612

Ehrlich I, Humeau Y, Grenier F, Ciocchi S, Herry C, and Lüthi A (2009) Amygdala inhibitory circuits and the control of fear memory. Neuron 62: 757-771.

Research group leader
Dr. Ingrid Ehrlich ingrid.ehrlich(at)uni-tuebingen.de Address

Center of Neurology
Hertie Institute for Clinical Brain Research
Independent Research Group "Physiology of Learning and Memory"

Otfried-Müller-Straße 25
72076 Tübingen

Phone: +49 (0)7071 29-89189
Fax: +49 (0)7071 29-25006

Open positions

 

Bachelors / Masters Thesis projects
Opportunities for projects available upon request

Lab Rotations / Internships
Placements available for students of the Graduate Training Centre of Neuroscience and students from other programs and universities upon request

Postdoc
We are looking for highly motivated candidates with expertise in electrophysiology, optogenetics, and/or imaging techniques.