Figure 1.
p75NTR-saporin induces specific lesions of the basal forebrain cholinergic neurons.
(A) Mean (± SEM) numbers of ChAT-positive neurons in basal forebrain nuclei and adjacent nucleus accumbens following intercerebroventricular application of mu-p75-SAP and the control toxin Rb-IgG-SAP. (B,C) Photomicrographs showing (B) ChAT-positive neurons in the medial septum (MS) and vertical limb of the diagonal band of Broca (VDB) and ChAT-positive terminal labelling in the hippocampus, anterior cingulate cortex and primary somatosensory cortex and (C) parvalbumin-positive neurons in the medial septum and vertical limb of the diagonal band of Broca following mu-p75-SAP or Rb-IgG-SAP treatment. (D) Mean (± SEM) numbers of parvalbumin-positive neurons in basal forebrain nuclei following intercerebroventricular application of mu-p75-SAP and the control toxin Rb-IgG-SAP. A specific loss of ChAT-positive neurons was detected in basal forebrain nuclei following mu-p75-SAP treatment (mu-p75-SAP vs. Rb-IgG-SAP, *p<0.001). Scale bars = 100 µm.
Figure 2.
Mice with cholinergic basal forebrain lesions have altered idiothetic navigation.
(A) Mean (± SEM) entrances to the shock zone, distance travelled and range of exploratory behaviour from the home zone during the 5 minute passive avoidance test, and scatterplot of the number of potential foot-shock events during this test. Control mice that received a foot-shock during training showed significantly fewer entrances to the shock zone on test than control mice that received no shock during training (* p<0.05). All mice that received a foot-shock during training travelled a significantly shorter distance during test than control mice (* p<0.05). No difference in the distance travelled during test was detected between mice that received a foot-shock during training. Lesioned mice explored further from the home (safe) zone than control mice that received a foot-shock during training (# p<0.05), and showed greater variability in the number of potential foot-shocks during test. (B) Representative tracking of exploratory behaviour during the 5 minute passive avoidance test for each of the four groups.
Figure 3.
Spatial and contextual fear memory, anxiety, sleep-wake cycles and motor performance of lesioned mice are normal.
(A) Mean (± SEM) percent context-elicited freezing 24 hours after fear conditioning training (5 random 0.8 mV foot-shocks). No difference in percent freezing during test was detected in lesioned mice compared to control mice that received foot-shocks,. (B) Mean (± SEM) time spent in the novel arm in the Y-maze. Lesioned mice spent an equivalent amount of time exploring the novel arm of the Y-maze to control mice. (C) Mean (± SEM) time achieved in the accelerating Rota-rod test. All mice successfully completed the 3 minute test with no falls recorded. (D) Mean (± SEM) initial time to enter, total time, and number of entries to the light area in the light/dark test of anxiety. No difference was detected between lesioned and control mice in the initial time taken to enter the light area or in the total time spent in the this area. However, lesioned mice made more entries into the light area during the 5 minute test than control mice (mu-p75-SAP vs Rb-IgG-SAP, *p<0.05). (E) Mean (± SEM) locomotor activity in 1 hour time bins over 36 hours incorporating 2 wake and 1 sleep cycles. No difference in locomotor activity was found between lesioned and control mice in either the wake or sleep cycle.