Somatosensory and Motor Research, 2011, 1–10, Early Online
ORIGINAL ARTICLE
Characteristics of synaptic connections between rodent primary
somatosensory and motor cortices
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MARY ROCCO-DONOVAN1, RADDY L. RAMOS2,3, SANDRA GIRALDO2, &
JOSHUA C. BRUMBERG1,2
1
Neuropsychology PhD Subprogram (Psychology), The Graduate Center, CUNY, New York, USA, 2Department of
Psychology, Queens College, CUNY, Flushing, New York, USA, and 3Department of Neuroscience & Histology,
New York College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA
(Received 15 June 2011; accepted 13 July 2011)
Abstract
The reciprocal connections between primary motor (M1) and primary somatosensory cortices (S1) are hypothesized to play
a crucial role in the ability to update motor plans in response to changes in the sensory periphery. These interactions provide
M1 with information about the sensory environment that in turn signals S1 with anticipatory knowledge of ongoing motor
plans. In order to examine the synaptic basis of sensorimotor feedforward (S1–M1) and feedback (M1–S1) connections
directly, we utilized whole-cell recordings in slices that preserve these reciprocal sensorimotor connections. Our findings
indicate that these regions are connected via direct monosynaptic connections in both directions. Larger magnitude
responses were observed in the feedforward direction (S1–M1), while the feedback (M1–S1) responses occurred at shorter
latencies. The morphology as well as the intrinsic firing properties of the neurons in these pathways indicates that both
excitatory and inhibitory neurons are targeted. Differences in synaptic physiology suggest that there exist specializations
within the sensorimotor pathway that may allow for the rapid updating of sensory–motor processing within the cortex in
response to changes in the sensory periphery.
Keywords: Barrel cortex, motor cortex, EPSPs, feedforward, feedback, cortico-cortical connections
Introduction
Both sensory and motor cortices contain topographic
maps (Woolsey 1952; Li and Waters 1991). Previous
anatomical studies have shown that direct, somatotopically organized reciprocal connections exist
between these areas in the rodent (Porter and
White 1983; Miyashita et al. 1994; Hoffer et al.
2003), and that the cell bodies of the cortico-cortical
efferents from S1 to M1 are located primarily in
infragranular layers (Izraeli and Porter 1995). In vivo
physiological studies have revealed strong monosynaptic inputs onto M1 efferent neurons originating
from S1 (Ghosh and Porter 1988). In fact, greater
than half of all projection neurons in the infragranular layer of M1 receive direct inputs from S1
(Zarzecki 1989). Functionally, in primates, inactivation of these inputs can result in disruption of motor
acts such as chewing (Lin et al. 1998), fine motor
coordination, sustained muscle contractions, appropriate grip force, and the ability to determine the
weight of an object (Johansson and Westling 1984;
Hikosaka et al. 1985; Brochier et al. 1999). Changes
in the sensory environment are thought to be relayed
via an intracortical pathway and not via direct
connections from that thalamus based on in vivo
latency analyses (Blum et al. 1968; Herman et al.
1985; Farkas et al. 1999). Thus, sensorimotor
interactions enable M1 and S1 to have adaptive
responses to changes in the periphery. Despite this
pathway’s critical role in modulating ongoing motor
Correspondence: J.C. Brumberg, PhD, Department of Psychology, Queens College, CUNY, 65–30 Kissena Boulevard, Flushing, NY 11367, USA.
Tel: þ1 718 997 3541. Fax: þ1 718 997 3257. E-mail: joshua.brumberg@qc.cuny.edu
ISSN 0899–0220 print/ISSN 1369–1651 online ß 2011 Informa Healthcare Ltd.
DOI: 10.3109/08990220.2011.606660
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M. Rocco-Donovan et al.
plans, little is known about the synaptic basis of these
interactions or the intrinsic properties of the neurons
involved.
The functional dynamics of feedforward and
feedback connections have been widely studied
within the visual system. These studies have shown
that feedforward and feedback connections often
vary in their laminar distribution and their synaptic
targets (Lund et al. 1975; Weller and Kaas 1983;
Johnson and Burkhalter 1996). Neurons involved in
these pathways have demonstrated differences in
responses to evoked stimuli in vitro (Shao and
Burkhalter 1996) and to stimuli presentation
in vivo (Angelucci and Bressloff 2006). Within the
sensorimotor system, S1 neurons projecting to M1
have receptive field characteristics that differentiate
them from other neurons (Sato and Svoboda 2010),
but the manner in which their responses impact
neurons in M1 are unknown. Characterizing the
components of these pathways and their function is
an important step towards understanding how the
brain translates sensory input into motor responses
and how changes in motor activity can influence
sensory neurons.
Materials and methods
All experiments were performed on CD-1 mice
(postnatal day 14–21) of either sex (Charles River
Laboratories, Wilmington, MA, USA). All experiments were performed in accordance with the
Institutional Animal Care and Use Committee
guidelines of Queens College, CUNY and the
National Institutes of Health.
Preparation of tissue for in vitro recording studies
Mice were anesthetized and the brain was quickly
removed and sectioned at 350 mm in the sensorimotor plane as previously described (Rocco and
Brumberg 2007) in chilled, oxygenated artificial
cerebral spinal fluid (ACSF) solution (in mM: 124
NaCl, 2.5 KCl, 2 MgSO4, 1.25 NaH2PO4, 1.2
CaCl2, 26 NaHCO3, 10 dextrose). Sensorimotor
sections were kept in oxygenated ACSF at 34 C for
at least 1 h before the start of the experiment.
Whole-cell recordings
Cells were visualized with infrared differential interference contrast optics (Olympus BX51WI).
Intracellular recording electrodes were pulled on a
microelectrode puller (Sutter P-87) resulting in a
final resistance of approximately 3 MV. Electrodes
were filled with (in mM) 120 KGlu, 10 NaCl, 20
KCl, 10 HEPES, 2 Mg-ATP, 0.3 Na-GTP, 0.5
EGTA, and 0.3–1% biocytin (wt/vol) for subsequent
visualization of the neurons. Cells were recorded
using current clamp methods as previously described
at room temperature (Ramos et al. 2008). Once a
stable recording was obtained (resting Vm555 mV,
ability to generate action potentials in response to a
depolarizing current pulse), cell intrinsic properties
were assessed. Resting membrane potential was
determined by measuring the membrane voltage in
the absence of current input. Intrinsic properties
were determined by quantifying responses to a series
of 500 ms steps (ranging from 300 to 300 pA)
applied from rest. To calculate action potential
characteristics, we analyzed responses of cells to
threshold currents for their generation. The input
resistance ratio (Rin ratio) was calculated based on
responses to a 500 ms step current of 30 pA. The
value is equal to the resistance at the maximum
hyperpolarized value divided by the resistance at
100 ms prior to the stimulus offset. The slope of the
firing vs. current (FI) relationship was determined by
analyzing responses of cells to threshold currents for
activating action potentials to responses twice the
threshold value. Once intrinsic properties were
assessed, synaptic response data were collected by
placing a bipolar stimulating electrode (1 M
,
FHC Inc., Bowdoin, ME, USA, Figure 1A) in the
infragranular layers of the whisker representation in
one area (e.g., M1), while simultaneously recording
in whole-cell configuration in the reciprocal area
(e.g., S1). A response threshold was determined by
stimulating with a series of 100 ms current pulses
(ranging from 1 mA to 10 mA) until a consistent
response was observed in response to the electrical
stimulation (see Figure 1B). Typically, 55 mA pulses
were used, and larger magnitudes were used to test if
non-responsive cells were truly non-responsive. If a
response was not observed to a single stimulus pulse,
a train of three pulses was then applied at various
frequencies (10–100 Hz). Final parameters were
noted and the responses to stimulation at 110% of
the minimal intensity necessary to evoke a postsynaptic response were used for analyses. Analyses
were performed on averages of 10 traces to ensure
reliability. For each identified connection a coefficient of variation analyses was performed (Berry and
Pentreath 1976; Faber and Korn 1991), wherein CV
(coefficient of variation) ¼ /, where is the standard deviation of response latency (in ms) and is
the mean response latency (in ms). Connections that
had values of CV 10% were assumed to be reflective of a monosynaptic connection. Direct comparisons between cells were only conducted between
those with identical stimulus parameters.
Four synaptic response categories were identified
based on individual cell responses to stimulation in
the reciprocal area: (1) short latency, presumed
monosynaptic connections that had little jitter
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In vitro sensorimotor connections
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Figure 1. The sensorimotor slice. Experimental setup post-fixation (A); a stimulating electrode was placed in S1 and wholecell recordings were obtained in M1. Cartoons above slice represent a train of three stimuli applied to S1 and the postsynaptic responses recorded in response within M1. Note barrels in S1 adjacent to the stimulating electrode and the
biocytin-filled neurons in M1 (black dots below cartoon of pipette), horizontal lines indicate where harp strings impacted the
slice. Minimal electric stimulation (B) resulted in consistent synaptic responses in either area (M1 top, S1 bottom); note lack
of synaptic jitter to identical stimuli in the overlays (each individual trace is an independent color), an average of 10 stimulus
presentations on the right. Arrows indicate stimulus onset.
(values of CV 10%) and occurred 25 ms following the stimulus (Figure 1B), (2) long latency,
presumed polysynaptic connections without a shortlatency component, which occurred425 ms following
the stimulus, (3) both, includes short- and long-latency
responses, and (4) no response. Long-latency responses
were unlikely due to antidromic stimulation since
deactivation of the stimulation site with muscimol,
which would not impact antidromic activation,
abolished all responses in the target area (Rocco
and Brumberg 2007), but are most likely due to
either polysynaptic activation and/or activation of
synapses mediated by metabatropic receptors (e.g.,
Covic and Sherman 2011).
Neuronal reconstruction
Following recording sessions, slices were transferred
to a 4% paraformaldehyde solution in 0.1 M
Phosphate Buffer for subsequent biocytin histochemistry (Ramos et al. 2008). Biocytin-filled cells from
whole-cell recordings were reconstructed for morphological analysis using the Neurolucida software
program (version 8.0, MicroBrightField Inc.,
Williston, VT, USA). Tracing of soma and dendrites
was done with an oil immersion objective (60, 1.4
N.A.) and analyzed using NeuroExplorer (a component of Neurolucida). Specifically, soma shape and
perimeter were quantified, as well as dendritic
parameters such as quantity, length, and branching
patterns.
Data analysis
Off-line analyses were performed using Clampfit 9.2
(Molecular Devices, Sunnyvale, CA, USA). Pairwise
comparisons were made post hoc using Fisher’s Least
Significant Difference tests. Cells were categorized
based on their response to the stimulus. T-tests were
used for comparisons between groups. A power
analysis was conducted to determine necessary
sample sizes; we assumed ¼ 0.8, ¼ 0.05, ¼ 0.1.
The resultant analyses suggested group sizes based
on estimated means from pilot data (Donovan et al.
2008) were 17. The Mann–Whitney test was used to
compare synaptic response results due to unequal
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M. Rocco-Donovan et al.
variance and 2-tests were used to compare population distributions between different groups.
Statistical analyses were done with Statistica
(StatSoft, Tulsa, OK, USA). Data are represented
as population means 1 SEM.
Results
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Direct connections are observed between S1 and M1
Once stable recordings were obtained and the
intrinsic membrane properties were assessed for a
given cell (see below), electrical stimulation was
applied to the reciprocal area via a bipolar electrode
(Figure 1) and any resulting post-synaptic response
was recorded. Despite the distance (3 mm)
between the two regions, short-latency responses
were observed in both regions following stimulation
in the reciprocal area confirming that this slice
preparation retains functional connections between
S1 and M1.
Overall, M1 cells (18 of 20) were more responsive
than S1 cells (18 of 33) to stimulation in the
reciprocal area (p50.01, Figure 2A). In addition,
cells in M1 (16 of 20) were more likely to have shortlatency responses to stimulation in the reciprocal area
than S1 cells (10 of 33). Short-latency responses
were characterized by little-to-no jitter in their
latencies or amplitudes (see Figure 1B). Cells in S1
had a higher proportion (8 of 33) of cells showing
purely long-latency responses than those in M1 (2 of
20), suggesting that it may be more difficult to target
the subpopulation of S1 neurons that receive shortlatency M1 inputs or that inputs in the feedback
direction are less numerous than those in the
feedforward direction. Interestingly, there was little
evidence of IPSPs (inhibitory post-synaptic potentials) in our recordings, suggesting that our stimulation resulted in only subthreshold responses
preventing the initiation of disynaptic inhibition.
Furthermore, fibers of passage are likely not underlying these results given that muscimol application at
the stimulation site prevents activation in the target
region (Rocco and Brumberg 2007). These results
indicate that cells receiving feedforward inputs (M1
cells) have a higher synaptic response probability and
suggest that M1 signals may be easily modifiable by
changes in the sensory environment conveyed by
these S1 inputs.
Synaptic properties of the S1–M1 pathway
Differential responsiveness of S1 and M1 cells is also
evidenced by comparing both the number of cells in
Figure 2. Short-latency inputs are more prevalent in M1. Two types of responses were observed following stimulation:
short- and long-latency responses which were seen in the average trace of 10 stimuli applied to S1 with recordings in M1
(inset in A, scale bar: 2.5 mV, 100 ms). Neurons were characterized as receiving short-, long-latency, or both types of
responses (see text). Neurons in M1 were more likely to receive inputs from S1 then the reciprocal relationship. Numbers in
bars indicate the number of cells in each category indicated out of S1 ¼ 33 and M1 ¼ 20 total recordings (A). Arrows point to
typical direct and indirect responses. S1 inputs to M1 were of larger magnitude (B) each direct, short-latency, response is
plotted on an arbitrary axis (inset is the average of 10 stimuli presentations). The distribution of EPSP latencies (C) and
population average (inset, bars represent population means 1 SEM) demonstrate that M1 feedback to S1 arrives sooner,
but is of smaller magnitude (D, bars represent population means 1 SEM). p50.05, p50.01.
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In vitro sensorimotor connections
each area that directly responded to low intensity
stimulation (single pulse55.0 mA), and the average
magnitude of the short-latency responses of these cells
(Figure 2B). Of the 33 sampled S1 cells, only 4 cells
showed a reliable short-latency response to low
intensity stimulation in M1 with an average magnitude of 2.62 0.85 mV. Conversely, of 20 M1 cells
sampled, 9 cells directly responded to low intensity
stimuli with a significantly higher average amplitude
response of 33.29 8.64 mV (p50.05; Figure 2D).
The variance in response may be reflective of
recordings done at room temperature that can lead
to small amplitude responses and increases in failure
rates (Kidd and Isaac 2001; Volgushev et al. 2004;
Ali et al. 2007). Coefficient of variation analysis on
these short-latency connections revealed that all those
cells in M1 that received short-latency responses had a
CV 10%; similarly, the S1 cells had a CV 8% that
strongly suggests that this class of connections is
indeed monosynaptic.
Although their distributions overlapped, differences were observed in the average time to peak of
short-latency synaptic responses onto S1 and M1 cells
(Figure 2C). When M1 was stimulated with a single
pulse of less than 5.0 mA of current, cells in S1 had
an average latency (time to peak) of 19 0.50 ms
(range 10–24 ms), which was faster than the response
latency observed in M1 cells when similar stimulation was applied to S1 (106 31 ms; p50.01; range
50–215 ms). Assuming a 3 mm separation between
the stimulation and recording sites, the axons projecting from S1 to M1 have an average transmittal
5
time (including the synaptic delay) of 0.03 m/s
compared to a speed of 0.16 m/s in the reverse
direction. The relatively long latencies observed in
both directions may be reflective of the age of our
animals but extracellular recordings from sensorimotor slices from adult animals (Rocco and
Brumberg 2007) demonstrated similar latencies.
Moreover, our study was conducted at room temperature in contrast to many in vivo studies (e.g.,
Farkas et al. 1999), which slows down conduction
velocities. Similar to our results, Farkas et al. (1999)
reported a small magnitude short-latency response
(likely due to direct thalamic input) followed by a
much larger response that peaked at 175 ms post
stimulus that is consistent with our in vitro findings.
These findings indicate that the feedforward input to
M1 results in a larger magnitude and slower response
than the feedback input to S1. These results are in
agreement with our previous study that found
smaller axon diameters in the feedforward pathway
that may provide the explanation as to why this
pathway has longer response latencies (Rocco and
Brumberg 2007).
Intrinsic properties of responsive and non-responsive
cells
Intrinsic membrane and firing properties of both M1
and S1 neurons were assessed identically by quantifying responses to a series of step currents of 500 ms
duration (Figure 3). Firing properties as well as
synaptic stimulation data were obtained from the
Figure 3. M1 inputs into S1 target multiple neuronal phenotypes. Reconstructions (left) of biocytin-filled fast spiking
(middle, response to a 160 pA, 500 ms in duration current pulse) non-pyramidal (A) and regular spiking (response to a
100 pA, 500 ms in duration current pulse) pyramidal neurons (B) from S1 that responded to M1 stimulation (right, traces
represent average of 10 stimulation presentations, arrows represent stimulation onset). Scale bars are the same for both top
and bottom traces.
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M. Rocco-Donovan et al.
Figure 4. Intrinsic properties of targeted neurons. (A) Representative first action potentials from S1 and M1 neurons
receiving direct input from the reciprocal area (action potential generated by a 60 pA pulse). S1 neurons have larger
magnitude action potentials (B), Rin ratios (C), with smaller magnitude after-hyperpolarizations (D, mAHP). Box plots
represent the 25–75% quartiles, lines represent median (solid) and mean (dashed) values and the error bars represent 5th
and 95th percentiles. p50.01.
majority of cells recorded from S1 (31 of 33) and all
cells recorded from M1 (20 of 20). All cells were
categorized by their spike pattern according to
previously published results (McCormick et al.
1985; Kawaguchi 1993). The majority of cells
recorded in S1 were found to be regular spiking
(RS, 28 of 31). A few fast spiking (FS) cells were
observed (2 of 31) and one cell in this area was
intrinsically bursting. A large portion of the cells
recorded in M1 were also found to be RS (12 of 20).
Additionally, low threshold spiking (LTS, 6 of 20)
and fast spiking (2 of 20) cells were also observed
in M1. While we were not able to systematically
sample from different populations of cells, our
sample does contain a variety of cell types that
would be expected to be encountered in these two
areas based on the literature (McCormick et al. 1985;
Kawaguchi 1993).
The majority of RS cells recorded in S1 (17 of 28)
were found to be responsive to stimuli in the reciprocal area. Approximately half of these responsive RS
cells (9 of 17) showed a short-latency response. Of the
three non-RS S1 cells, only one was responsive to M1
stimulation; this cell showed a short-latency response.
Nearly all of the RS cells found in M1 responded to
stimuli in S1 (11 of 12), almost all of which were shortlatency responses (10 of 11). The response probabilities of the LTS cells (5 of 6) and the FS cells (2 of 2)
in M1 were also very high. All of the FS cells (2 of 2)
and all but one of the LTS cells (4 of 5) showed a shortlatency response. These results indicate that in both S1
and M1, many cell types are responsive to stimulation
in the reciprocal area.
The cell intrinsic properties of RS cells that fell
into the both response category in S1 (n ¼ 17) and M1
(n ¼ 12) are compared in Figure 4. Responsive cells
in S1 had significantly greater spike amplitudes
(Figure 4B, p50.001) and input resistance ratios
(Figure 4C, p50.009). M1 responsive cells had
significantly larger magnitude after-hyperpolarization
(AHP) than S1 responsive cells (Figure 4D,
p50.001). S1 and M1 responsive cells did not
differ significantly on measures of resting membrane potential, spike threshold, AHP duration,
spike rise-time, or slope of the FI curve (values of
p40.05). These results suggest that within our
sample, responsive cells in S1 and M1 were comparable on most intrinsic membrane measures, but
differ physiologically in some aspects of their firing
properties such as action potential and AHP
amplitudes.
Laminar location of recovered cells
Given the limited area of recording sites within each
sensorimotor slice and the physical limitations of the
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In vitro sensorimotor connections
recording setup, we were unable to systematically
target cells by their relative laminar location or their
relationship to the somatotopy in either area.
However, the position of these cells within the
cortical plate was of interest, as previous studies
have shown variability in the laminar distribution of
feedforward vs. feedback cells (Rockland and Pandya
1979; Rockland and Virga 1989). To obtain this
information, we measured the relative locations of
recovered somata in both areas, and used this
information to examine the relationship between
the presence of a synaptic response and position
within the cortical plate.
Morphological data, including laminar location,
were collected for each of the recovered cells.
Laminar locations of cell bodies were determined
in S1 (21 of 33) and M1 (14 of 20). For all recovered
cells, measurements were made to determine the
cells’ relative location within the cortex. Post hoc
determination of the average distance between the
stimulating electrode and the recorded cell was
2.97 0.17 mm across all experiments (n ¼ 35
cells). We measured the location of the barrels
within the cortical plate and used this measure as a
reference point in determining the relative cell
depths. Cell location was reported as the relative
location of the soma between the white matter and
pia on a scale from 0 to 1, in which the white matter
border is 0 and the pial surface is 1. On average, the
barrel region within the S1 portion of the slice
occupied from 0.40 to 0.60 (based on cytochrome
oxidase staining, data not shown). Based on this
approximation, the cells whose somas lie within this
region in S1 were considered to reside within layer 4.
Cells whose somas were below 0.40 were considered
infragranular and those above 0.60 were considered
supragranular (see Figure 5). The majority of the
responsive cells recovered within S1 (15 of 21) were
in the infragranular layers, followed by cells in layer 4
(5 of 21) and only one of the recovered cells in S1
was located in the supragranular region. Using
optogenetic techniques it has been shown that there
are some M1 inputs into layer 1 in S1 that target the
apical dendrites of layer 2/3 and 5 neurons. But in
comparison there was much larger feedback
responses targeted to the basilar dendrites and
somata of neurons residing in layer 5 (Petreanu
et al. 2009), which is consistent with in vivo recordings from M1 in cats (Zarzecki 1989).
For measurements in M1, we divided the cortex
into three equal parts, lower third (0–0.32), middle
third (0.33–0.66), and upper third (0.67–1.00). The
lower third was considered the infragranular layers
and the upper third the supragranular layers. The
majority of recovered M1 cells (11 of 14) were in the
infragranular layers (lower third). The remaining M1
cells (3 of 14) were in the middle third. For both S1
7
Figure 5. Laminar location. Neurons that received either
direct, indirect, or both types of synaptic inputs were
located relative to the cortical plate. The white mater
(WM) is located towards the bottom of the graph (0 on the
y-axis) and the pia (1.0) towards the top. Dotted circles
represent approximate location of the S1 barrels. Bars
represent population means and 1 SEM
and M1 the probability of finding a post-synaptic
response following stimulation in the reciprocal area
was highest in the infragranular layers.
Morphological categorization of recovered cells
A large proportion of the S1 cells were recovered
(21 of 33), most of which (16 of 21) were also able to
be reconstructed (see Figure 3). The majority of cells
recorded from M1 (14 of 20) were recovered, of
which 11 of 14 were able to be morphologically
reconstructed. Of the 16 fully reconstructed cells in
S1, 15 had pyramidal cell bodies. Of the 11 cells
recovered from M1, 4 were pyramidal in shape and 7
were non-pyramidal. Interestingly, unlike the visual
system, responsive cells did not appear to be
restricted to a particular morphological cell type
(Shao and Burkhalter 1996). Observing the dendritic
architectures of the responsive neurons revealed a
variety of phenotypes (see Figure 3). Quantitative
analysis of somatic (area, aspect ratio, etc.) and
dendritic parameters (quantity, length, branching
patterns, etc.) did not reveal significant differences
between the two areas or within response groups in
either area. These results are consistent with in vivo
findings that demonstrate that multiple classes of M1
efferent neurons receive inputs from S1 (Zarzecki
1989) and vice versa.
Discussion
Many studies have successfully used in vitro preparations to investigate connectivity between distant
brain locations (Agmon and Connors 1991; Shao
and Burkhalter 1996; Cruikshank et al. 2002). This
is the first in vitro study using whole-cell recording
techniques to describe and quantify the synaptic
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M. Rocco-Donovan et al.
connections between S1 and M1. Despite the
3 mm separating stimulation and recording sites
in our preparation, we can conclude that shortlatency presumably monosynaptic connections exist
in both the feedforward and feedback pathways of the
sensorimotor system in the mouse. A limitation of
our preparation is the lack of thalamic inputs that
project to both areas and may play an important
role in modulating S1–M1 interactions, but our
findings that there are intrinsic differences between
neurons in the two areas is independent of any
thalamic inputs. Previous research has shown that
following chemical inactivation (Chakrabarti et al.
2008) or ablation (Farkas et al. 1999) of
whisker S1 there is an almost complete removal of
whisker-evoked responses in S1. These results
support the hypothesis that the feedforward inputs
to M1 from S1 are driving the majority of the
whisker-evoked
activity
observed
in
M1.
Furthermore, our results do show that there are
specific differences in the feedforward vs. feedback
pathways that potentially can be modulated by
extrinsic or local connections. Whole-cell recordings
revealed that multiple cell types in S1 and M1 are
responsive to stimuli from the reciprocal area. For
both pathways, the probability of finding a postsynaptic response following stimulation in the reciprocal area was highest in the infragranular layers,
which is consistent with the observed termination
patterns of the axonal projections. In comparing
synaptic responses under identical stimulation conditions, feedforward input from S1 to M1 resulted in
significantly larger responses, but with significantly
longer latencies than feedback responses. The faster
feedback connection may be important in providing
updated information about whisker position to S1
neurons.
Our results are consistent with previous findings
indicating that feedforward connections appear to be
stronger than feedback connections. In an in vitro
preparation containing V1 and the rodent homolog
of V2, activation of feedforward connections to V2
resulted in significantly larger amplitude EPSPs
(excitatory post-synaptic potentials) than those
resulting from feedback connections (Shao and
Burkhalter 1996). One explanation for these results
may be differences in the density of the projections
between the two areas. Feedback inputs to V1 of the
rodent are about 50% less numerous than feedforward inputs to V2 (Shao and Burkhalter 1996).
Similarly, significantly fewer projections were
observed in the feedback from area MT to V1 in
the primate when compared to the feedforward
direction (Maunsell and Van Essen 1983). Within
the auditory system, the connections between primary and secondary cortex have been investigated
using electrical stimulation and glutamate uncaging,
and direct inputs have been found between the two
areas that were mediated by either ionotropic or
metabatropic glutamate receptors, suggesting that
there may be two time scales of modulation between
cortical areas (Covic and Sherman 2011) as seen in
the present study. The long-latency responses
observed in the present recordings were consistent
over 10 stimulus presentations and thus even if due
to polysynaptic circuits they must be wired such that
they are continually activated or a result of activation
of metabatropic receptors.
It is not known if a specific topography exists for
the reciprocal S1–M1 connection, but S1 neurons
that project to M1 preferentially lie beneath the
septal areas (Chakrabarti and Alloway 2006) and
within M1, neurons that receive input from different
origins appear to be located within intermingled
patches (Zarzecki 1991; Zarzecki et al. 1993) and
perhaps neurons in these areas are more likely to
receive direct feedback connections. It appears that,
in general, M1 responses to sensory stimuli are
dependent on initial S1 processing. In vivo calcium
imaging has shown that a single, brief whisker
defection results initially in a strong depolarization
in S1 followed by subsequent M1 activation (Ferezou
et al. 2007). Significant reductions have also been
observed in M1 stimulus-evoked responses following
inactivation or ablation of S1 (Asanuma et al. 1980;
Farkas et al. 1999). Additionally, in rats, trimming
their whiskers from birth or during adulthood alters
the somatotopic organization and responses within
M1 (Huntley 1997). Behavioral data from primates
has shown that following either M1 or S1 inactivation
with muscimol (Brochier et al. 1999) there are
characteristic deficits on a motor control task. In
sum, these findings highlight the necessity of an
intact cortical sensorimotor loop in order to process
and complete sensorimotor tasks.
While neither M1 (Gao et al. 2003) or S1 (Harvey
et al. 2001) is necessary to produce whisking, the
feedforward projections sent from S1 to M1 may be
important in regulating whisking dynamics
(Kleinfeld et al. 2002). The functions of feedback
projections from M1 to S1 in general are not well
understood. In the whisker pathway, they may serve
to synchronize firing of cells that respond to similar
stimuli. In general, this process would serve to focus
the activation such that only a specific subset of cells
would be excited. Consistent with this is the finding
that M1 activation specifically excites corticothalamic neurons in S1 that are responsive to the
homotopic whiskers (Lee et al. 2008). In the
feedforward direction, distinct activation could
result in an alteration of whisker movements that
would allow for better discrimination on subsequent
whisk cycles.
In vitro sensorimotor connections
Acknowledgements
This work was supported by NS058758 and PSCCUNY 36-887 and 37-876 grants to J.C.B. and a
DSC grant to M.R.D. We thank Drs Stephan F.
Brumberg, Asaf Keller, Jonathan B. Levitt, Carolyn
L. Pytte, and Daniel Simons for helpful comments
on the paper.
Somatosens Mot Res Downloaded from informahealthcare.com by Dr. Joshua Brumberg on 09/13/11
For personal use only.
Declaration of interest: The authors have no
conflict of interests.
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