Perelman School of Medicine at the University of Pennsylvania

Dani Lab

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Our Research

The lab uses a variety of approaches in a rodent model to further our understanding and treatment of neurodegenerative diseases, mood disorders, and addiction.


Example research topics

To examine the role of specific neural pathways in alcohol and drug self-administration, we are using optogenetics in transgenic Long-Evans rats to control neurotransmitter release at specific target areas.

Three panel figure depicting the viral optogenetic schematic, staining and dopaminergic release in striatum
(A-B) We have microinjected viral vectors into the ventral midbrain to express light-sensitive proteins in VTA dopamine neurons that project from the midbrain to the striatum. (C) In rats expressing channelrhodopsin, an excitatory opsin protein, light stimulation at target regions in the ventral striatum causes a transient increase in extracellular dopamine levels as measured by in vivo microdialysis (Doyon, unpublished).

 

We showed in Thomas et al. (2018) and Ostroumov et al. (2016) that adolescent nicotine or acute stress exposure attenuates alcohol-induced dopamine signals and increases drinking in rodents. Both stress and nicotine cause midbrain circuitry changes via neuroendocrine signals that ultimately impair a chloride transporter and shift GABA inhibition toward excitation.

Stained dopamine neurons in the reward circuit
Dopamine neurons (green) in the reward circuit.

 

The role of dopamine in reward signaling is well known, but Broussard et al. (2016) showed that dopamine D1-like receptor activity in the hippocampus is necessary for retention of aversive memories. Our results indicate dopaminergic function within the hippocampus affects long-term synaptic potentiation associated with aversive memory retention.

Stained hippocampus section
Section of a mouse hippocampus infected with a virus expressing Channelrhodopsin 2 and implanted with an optetrode to control and record neuronal activity at the CA1 region. Recording electrode position can be seen by post-hoc lesion at the CA1 pyramidal field.
 

Commonly used techniques

  • Operant drug administration
  • In vivo microdialysis and high-performance liquid chromatography (HPLC)
  • In vivo and slice electrophysiology
  • Viral circuit mapping
  • Optogenetics
  • Behavioral pharmacology
  • Immunohistochemistry