Maturation of cortical input to dorsal raphe nucleus increases behavioral persistence in mice

  1. Nicolas Gutierrez-Castellanos
  2. Dario Sarra
  3. Beatriz S Godinho
  4. Zachary F Mainen  Is a corresponding author
  1. Champalimaud Research, Champalimaud Foundation, Portugal
  2. Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom
8 figures and 1 additional file

Figures

Figure 1 with 2 supplements
Top–down cortico-raphe connections develop over adolescence in mice.

(A) Schematic representation of a sagittal view of an Rbp4-ChR2 mouse brain illustrating top–down cortico-raphe afferents. Coronal slices containing the dorsal raphe nucleus (DRN) were obtained ex …

Figure 1—source data 1

Electrophygiological recordings and axonal quantification.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Changes in cortico-raphe connectivity over development are not explained by changes in the location of the recorded dorsal raphe nucleus (DRN) neurons.

(A) Example low magnification picture taken of a recorded DRN neuron and overlaid atlas inset used to determine its location. (B, C) Summary of the spatial location and connectivity of the recorded …

Figure 1—figure supplement 1—source data 1

Electrophysiological properties of DRN neurons and optogenetic controls.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig1-figsupp1-data1-v2.xlsx
Figure 1—figure supplement 2
Changes in cortico-raphe connectivity over development are not explained by changes in membrane properties of dorsal raphe nucleus (DRN) neurons or by differential ChR2 expression of ChR2 under the Rbp4 promoter over time.

(A) The input resistance of DRN neurons is comparable over time. (B) The fraction of putative 5-hydroxytryptamine (5-HT) neurons (capacitance >20 pF) and non-5-HT neurons (capacitance <20 pF) (Soiza-…

Figure 2 with 1 supplement
Adult mice persist longer than juveniles in exploiting a foraging patch.

(A) Illustration of the rodent foraging task. Water-deprived mice seek rewards by probing two nose-ports. (B) Randomly selected examples of poking behavior throughout a naive juvenile, naive adult, …

Figure 2—figure supplement 1
Description of mouse nose foraging behavior over the session progression and according to sex.

(A) Distribution of the trial durations for naive juveniles and naive adults (left) and for Caspase and tdTomato control mice (right). Note that the bimodality of the data visibly arises at the …

Figure 2—figure supplement 1—source data 1

Behavioral controls across experiments.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig2-figsupp1-data1-v2.xlsx
Figure 3 with 3 supplements
Animals lacking cortico-raphe projections show less behavioral persistence in exploiting a foraging patch.

(A) Schematic representation of the ablation strategy used for behavioral assessment. Retrogradely transporting AAV vectors expressing either the fluorescent reporter tdTomato (rAAV-tdTomato) or the …

Figure 3—source data 1

Cell loss and behavioral quantification in caspase and control mice.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig3-data1-v2.xlsx
Figure 3—figure supplement 1
Viral injections in the dorsal raphe nucleus (DRN) provide localized cortico-DRN axonal feedback and do not affect neuronal density.

(A) Example confocal images containing the DRN and adjacent structures for a control tdTomato and a Caspase injection (left and right, respectively) in which the native fluorescence of tdTomato …

Figure 3—figure supplement 1—source data 1

NeuN and tdTomato density in the DRN.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig3-figsupp1-data1-v2.xlsx
Figure 3—figure supplement 2
Labeling of Rbp4-expressing dorsal raphe nucleus (DRN)-projecting neurons with rAAV-tdTomato is consistent with cell density loss in mice injected with rAAV-Caspase3.

(A) Schematic representation of rAAV-tdTomato-dependent labeling of cortico-DRN-projecting neurons in Rbp4-Cre mice. (B) Quantification of layer 5 tdTomato labeled somas across the different …

Figure 3—figure supplement 2—source data 1

NeuN and tdTomato densities across cortical areas.

https://cdn.elifesciences.org/articles/93485/elife-93485-fig3-figsupp2-data1-v2.xlsx
Figure 3—figure supplement 3
Dorsal raphe projecting cortical neurons have dense collateral projections to the striatum.

(A) Schematic representation of rAAV-tdTomato-dependent labeling of cortico-dorsal raphe nucleus (DRN)-projecting neurons in Rbp4-Cre mice. (B) Schematic representation of axon collaterals from the …

Author response image 1
Author response image 2
Kernel density function of leaving times of control animals, in blue, and experimental animals, in red.

Solid and dashed lines indicate animal and group functions, respectively.

Author response image 3
K-means based categorization of each trial in short and long leaving times.

Individual control and experimental animals are colored with shades of blue and red respectively.

Author response image 4
Scatter plot of the difference in the frequency use of short and long leaving time for each animal.

Control and experimental animals are colored in blue and red respectively.

Author response image 5

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