Miniatured Microscopy solutions

Miniaturized fluorescence microscopy is a method that uses a lightweight and small footprint microscope to monitor and modulate large scale cellular activity in freely behaving animals.

  • Advantages
    • Record individual cell activity in a specific population of neuronal or glial cells using genetically encoded sensors
    • Map the spatial position of group of cells
    • Correlate functional and morphological cellular activity with animal behavior
    • Monitor the same population of cells over months
    • Modulate activity in a specific population by combining imaging with optogenetic manipulations using genetically encoded opsins
    • Compare the activity of two populations or take advantage of combinatory genetic labeling approaches when using two-color fluorescence microscopes
    • Combine microscope imaging with other modalities such as fluid injection, or fiber photometry using specialized implants.
  • Disadvantages
    • Heavier than photometry recording systems as the miniaturized microscope is attached to the animal during recording
    • Limited sampling depth, due to light scattering and absorption (1-photon epifluorescence imaging)
    • Invasive chronic implant

Solutions

Doric offers complete turn-key solutions that include all the necessary components for fluorescence imaging in freely behaving animals, from the implant to the software interface.

For deep brain single marker imaging, opt for the Twist-on efocus Microsopy systems available for green or red fluorescence imaging, and benefit of:

  • An intuitive and robust connection between the microscope body and the imaging cannula using the new twist-on mechanism (no pressure on the skull during connection, no tools required)
  • A precise electronic focus adjustment that allows to track the same cells over time and improves fluorescence signal and spatial resolution
  • The imaging cannula auto-alignment: the GRIN relay lens is always perfectly aligned with the microscope
  • A GRIN lens implant for each application: 1 mm of diameter GRIN lenses for a larger field of view when imaging superficial brain regions (cortex, hippocampus), or less invasive 0.5 mm of diameter GRIN lenses to image deeper structures (hypothalamus), prism tip option for lateral imaging and lower invasiveness
  • An optogenetic stimulation option that provides up to 55 mW/mm2 of yellow light (pulsed or continuous) at the tip of the implant
  • An enhanced durability with connectorized cables and a lightweight machined aluminium microscope body

To record simultaneously the activity of two populations labelled with two spectrally distinct fluorophores, the 2-color Fluorescence Microscopy systems should be considered. Doric’s 2-color microscope are highly miniaturized and integrate two independent image sensors optimized for GCaMP and Red fluorescence imaging.

If you are more interested in the superficial layers of the brain consider surface models of single-color or 2-color microscopes. Without the need of rod implants (e.g. GRIN lenses) surface microscopy is less invasive than deep-brain microscopes and has a larger field of view. Surface microscopes can also be combined with a glass prism to image brain structures up to 1.5 mm deep.


Comparison Table for Doric Lenses Miniature Microscopy systems
System Type Deep brain
1-color
Surface
1-color
Deep brain
2-color
Surface
2-color
Electronic focus Yes No No No
Optogenetic option Yes Yes No No
Fluid injection option Coming soon Yes Yes Yes
Rotary joint option Yes Yes Yes Yes

 


External References

 1.  A. Gengatharan et al. Adult neural stem cell activation in mice is regulated by the day/night cycle and intracellular calcium dynamics.
      Cell 184, 709–722 (2021).
 2.  A. Glas et al. Spaced training enhances memory and prefrontal ensemble stability in mice.
      bioRXiv (2020)

      Brain region: dorsomedial prefrontal cortex (dmPFC)
 3.  F. Fredes et al. Ventro-dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.
      Current Biology 31, 25–38.e5 (2021)
      Brain region: Ventral hilus; dorsal dentate gyrus
 4.  D. Rossier et al. A neural circuit for competing approach and avoidance underlying prey capture.
      bioRXiv (2020)
      Brain region: Lateral Hypothalamus (LHA)
 5.  P. Krzywkowski et al. Dynamic encoding of social threat and spatial context in the hypothalamus.
      eLife 9, e57148 (2020)
      Brain region: Hypothalamus (VMHvl)
 6.  C. Prévost-Solié et al. Superior Colliculus to VTA pathway controls orienting behavior during conspecific interaction.
      bioRXiv (2019)
      Brain region: Superior Colliculus (SC)
 7.  A. Glas et al. Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex
      Plos One (2019)
      Brain region: visual cortex (V1)
 8.  J.M. Patel et al. Sensory perception drives food avoidance through excitatory basal forebrain circuits.
      eLife 8, e44548 (2019)
      Brain region: basal forebrain (BF)
 9.  Fu et al. SatB2-Expressing Neurons in the Parabrachial Nucleus Encode Sweet Taste
      Cell reports 27 , 1650-1656 (2019)
      Brain region: parabrachial nucleus (PBN)
10. B. Roberts et al. Ensemble encoding of action speed by striatal fast-spiking interneurons
      Brain structure and function (2019)
      Brain region: dorsal striatum (DS)
11. S. Shin et al. Drd3 Signalling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction
      Neuron 97, 195–208 (2018)
      Brain region: lateral septum (LS)
12. E. Gallo et al. Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum.
      Nature Communication 9, 1086 (2018)
      Brain region: nucleus accumbens (NAc)
13. D.A. Evans et al. A synaptic threshold mechanism for computing escape decisions
      Nature 558 , 590–594 (2018)
      Brain region: dorsal periaqueductal gray (dPAG); medial superior colliculus(mSC)
14. T.C. Francis et al., Molecular basis of dendritic atrophy and activity in stress susceptibility.
      Molecular psychiatry 22, 1512–1519(2017)
      Brain region: nucleus accumbens (NAc)