with no obvious changes in the currents required to evoke PStF or the thresholds for conventional intracortical microstimulation (ICMS)
(fig. S15, A and B). We compared the PStF latencies from forelimb muscles after CST axon
stimulation in the ventral portion of the C5
dorsal column (DC) (Fig. 2H). Antidromic field
recordings from the motor cortex confirmed
CST activation in our stimulation paradigm
from this ventral stimulation site, but not from
the dorsal portion of the DC, where ascending
sensory fibers reside (Fig. 2, I and J, and fig.
S16). PStF latencies evoked through ventral DC
stimulation (CST) in PlexA1fl/fl;Emx1-Cre mice
were significantly shorter than those observed
in PlexA1 fl/fl mice (Fig. 2, K to N), whereas stim-
ulation of the dorsal DC showed no differences
in evoked EMG responses between control and
PlexA1fl/fl;Emx1-Cre mice (fig. S17). Furthermore,
we found that current amplitudes used to evoke
EMG responses through either the dorsal DC
(afferent fibers) or the ventral DC (CST) were
similar between control and PlexA1fl/fl;Emx1-Cre
mice (fig. S15, C and D).
CM connections are critical for fine manual
dexterity in primates (11, 12). Rodents show a
limited degree of manual dexterity without CM
connections by using coordinated paw move-
ments to manipulate food pieces (13). To mea-
sure manual dexterity, we performed the capellini
handling test (Fig. 3A and fig. S18, E to G) with
mice that had received AAV1-Cre bilateral mo-
tor cortex injections at P2 (PlexA1fl/fl;AAV1-Cre
mice), which produces similar developmen-
tal pruning defects as those observed in the
Emx1-Cre–mediated mutants (fig. S18, A to D).
PlexA1fl/fl;AAV1-Cre mice ate the capellini signif-
icantly faster than PlexA1fl/+;AAV1-Cre mice on
all testing days (Fig. 3B, fig. S18H, and movies
S1 to S4) and exhibited significantly higher paw
adjustment rates on all four testing days as
compared with PlexA1fl/+;AAV1-Cre mice (Fig.
3C and fig. S18I). In addition, PlexA1fl/fl;AAV1-
Cre mice displayed fewer atypical handling pat-
terns than did PlexA1fl/+;AAV1-Cre mice (Fig. 3D
402 28 JULY 2017 • VOL 357 ISSUE 6349 sciencemag.org SCIENCE
Fig. 2. Functional CM connections in adult PlexA1fl/fl;Emx1-Cre mice.
(A) Schematic diagram of experiment to examine PStF in adult mice
(3 months or older). EMG recordings from contralateral flexor carpi radialis
and biceps brachii muscles. (B and C) Contralateral PStF from (B)
control (PlexA1fl/fl) and (C) mutant (PlexA1fl/fl;Emx1-Cre) mice. Dotted line
indicates the onset of the EMG response in the mutant; arrows indicate
EMG onsets. (D and E) Frequency distributions of contralateral
PStF values from (D) control (PlexA1fl/fl, n = 6; wild-type, n = 3) and (E)
PlexA1fl/fl;Emx1-Cre (n = 8) mice. (F) PStF latencies after motor cortex
stimulation in PlexA1fl/fl (41 stimulation sites; median delay = 11.34 ms)
and PlexA1fl/fl;Emx1-Cre (37 stimulation sites; median delay = 13.88 ms)
mice. ***P < 0.001. (G) Cumulative frequency distribution histogram. gray
line, PlexA1fl/fl;Emx1-Cre mice; black line, PlexA1fl/fl mice. ***P < 0.001.
(H) Schematic diagram of DC electrical stimulation-evoked muscle PStF.
(I) Section from a DC stimulation experiment, showing the three electrode
locations used to evoke M1 antidromic responses. (J) Electrical stimulation
of the ventral DC evokes an antidromic field potential in the motor cortex. 1,
Dorsal DC stimulation, where afferent fibers are located; 2, ventral DC
stimulation (where CST fibers are located); and 3, stimulation at the level
of the central canal (K and L) PStF traces derived from average EMG responses
evoked by ventral DC sites in (K) PlexA1fl/fl and (L) PlexA1fl/fl; Emx1-Cre mice.
Dotted line indicates the onset of the EMG response in the mutant; arrows
indicate EMG onsets. (M) PStF latencies in PlexA1fl/fl (44 sites from
8 animals; median delay = 4.88 ms) and PlexA1fl/fl;Emx1-Cre (36 sites from
6 animals; median delay = 3.66 ms) mice. ***P < 0.001. (N) Cumulative
frequency distribution plot of PStF latencies from PlexA1fl/fl;Emx1-Cre (gray
line) and PlexA1fl/fl mice (black line). Arrows indicate the onsets of EMG
responses [(B), (C), (K), and (L)]. ***P < 0.001.