Differential Effects of Aging on Fore– and Hindpaw Maps of Rat Somatosensory Cortex

Getting older is associated with a decline of cognitive and sensorimotor abilities, but it remains elusive whether age-related changes are due to accumulating degenerational processes, rendering them largely irreversible, or whether they reflect plastic, adaptational and presumably compensatory changes. Using aged rats as a model we studied how aging affects neural processing in somatosensory cortex. By multi-unit recordings in the fore- and hindpaw cortical maps we compared the effects of aging on receptive field size and response latencies. While in aged animals response latencies of neurons of both cortical representations were lengthened by approximately the same amount, only RFs of hindpaw neurons showed severe expansion with only little changes of forepaw RFs. To obtain insight into parallel changes of walking behavior, we recorded footprints in young and old animals which revealed a general age-related impairment of walking. In addition we found evidence for a limb-specific deterioration of the hindlimbs that was not observed in the forelimbs. Our results show that age-related changes of somatosensory cortical neurons display a complex pattern of regional specificity and parameter-dependence indicating that aging acts rather selectively on cortical processing of sensory information. The fact that RFs of the fore- and hindpaws do not co-vary in aged animals argues against degenerational processes on a global scale. We therefore conclude that age-related alterations are composed of plastic-adaptive alterations in response to modified use and degenerational changes developing with age. As a consequence, age-related changes need not be irreversible but can be subject to amelioration through training and stimulation

Differential effects of aging on fore- and hindpaw maps of rat somatosensory cortex

Getting older is associated with a decline of cognitive and sensorimotor abilities, but it remains elusive whether age-related changes are due to accumulating degenerational processes, rendering them largely irreversible, or whether they reflect plastic, adaptational and presumably compensatory changes. Using aged rats as a model we studied how aging affects neural processing in somatosensory cortex. By multi-unit recordings in the fore- and hindpaw cortical maps we compared the effects of aging on receptive field size and response latencies. While in aged animals response latencies of neurons of both cortical representations were lengthened by approximately the same amount, only RFs of hindpaw neurons showed severe expansion with only little changes of forepaw RFs. To obtain insight into parallel changes of walking behavior, we recorded footprints in young and old animals which revealed a general age-related impairment of walking. In addition we found evidence for a limb-specific deterioration of the hindlimbs that was not observed in the forelimbs. Our results show that age-related changes of somatosensory cortical neurons display a complex pattern of regional specificity and parameter-dependence indicating that aging acts rather selectively on cortical processing of sensory information. The fact that RFs of the fore- and hindpaws do not co-vary in aged animals argues against degenerational processes on a global scale. We therefore conclude that age-related alterations are composed of plastic-adaptive alterations in response to modified use and degenerational changes developing with age. As a consequence, age-related changes need not be irreversible but can be subject to amelioration through training and stimulation

Footprint characteristics of the hindpaw.

<p>Mean values±SD of the gait parameters print area (A), lengths of the print (C), stride-lengths (B) and track-widths (D) for the young (black) and the aged rats (red), * p<0.01. (A+C): In contrast to the prints obtained from the forepaws (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003399#pone-0003399-g004" target="_blank">Fig. 4</a>), the limb-specific parameters print area and the lengths of the prints of the hindpaw were significantly increased in old animals. (B+D): As in the forepaw (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003399#pone-0003399-g004" target="_blank">Fig. 4</a>), for the global parameters we found decreasing stride-lengths and increasing track-widths for the hindpaw in the aged animals.</p

Averaged latencies of young and old rats.

<p>(A) Averaged peak response latencies of neurons from fore- and hindpaw-representations of young (black) and aged (red) animals are shown. Error bars indicate the SEM. * p<0.01. (B) Normalized age-related lengthening of peak response latencies. The lengthening was 24.4% for the forepaw and 36.2% for the hindpaw. In contrast to the parameter RF-size the lengthening of latencies was similarly affected in cortical neurons of fore- and hindpaw-representation.</p

Average RF-sizes of young and old rats.

<p>(A) Average RF-sizes of the fore- and hindpaw of young (black) and aged (red) animals are shown. Error bars indicate SEM. * p<0.01, ** p<0.001. (B) Normalized age-related RF-enlargement. The increase of RF-size was 22% for the forepaw and 190% for the hindpaw. Although we found that RFs were enlarged on both the fore- and the hindpaw of old animals, the effects of aging on the RF-size was substantially stronger on the hindpaw than on the forepaw. (C) Mean values (±SEM) of RF-length. ** p<0.001. RF-lengths was only measured for hindpaw RFs of young (black) and old (red) rats. Analogous to the RF-size determined by handplotting we found a significant increase of RF-lengths for the old animals.</p

Cutaneous receptive fields (RFs) of the fore- and hindpaw.

<p>Typical examples of cutaneous receptive fields (RFs) of neurons recorded in the fore- and hindpaw representation of a rat aged 4 months (A, upper panel) and a rat aged 30 months (B, lower panel). (A) RFs on the forepaw of young rats were very small (left) usually comprising only small parts of a digit or a single digit or pad. RFs on the hindpaw of young rats (right) were slightly larger than on the forepaw, typically consisting of a single digit or parts of a digit. On the more proximal area of the hindpaw, RFs comprised single pads and larger skin areas in the range of the heel. (B) RFs on the forepaw of old rats (left) were only slightly enlarged as compared to young animals. Typical RFs comprised parts of a digit or a single digit or pad. In contrast to the forepaw, RFs located on the hindpaw (right) of old rats were severalfold enlarged. RFs in old rats were characterized by representations of multiple digits and pads and by substantially enlarged RFs in the proximal parts of the paw.</p

Footprint characteristics of the forepaw.

<p>Mean values±SD of the gait parameters print area (A), lengths of the print (C), stride-lengths (B) and track-widths (D) for young (black) and aged rats (red), * p<0.01. (A+C): The limb-specific parameter print area was reduced and print lengths remained unchanged in aged rats, which was not the case for the hindpaw (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003399#pone-0003399-g005" target="_blank">Fig. 5</a>). (B+D): The global walking parameters stride-lengths decreased and track-widths increased in aged rats. This was also observed for the hindpaw (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003399#pone-0003399-g005" target="_blank">Fig. 5</a>).</p

Calculation of RF-length.

<p>(A) We used a fixed set of 4 electromagnetic stimulators positioned along the proximal-distal axis of the hindpaw. The first one was positioned on a digit (p1), stimulators 2 and 3 were positioned on the pads and the 4^th stimulator was on the more proximal portion of the hindpaw (p4). Tactile stimulation was carried out one after the other at each position. Only RFs were analyzed whose RF were according to hand-plotting localized on a digit. (B) The neuronal response after stimulation at position 1 was set as 100%. The neuronal responses obtained from stimulation at the other positions were normalized and plotted versus the distance from the RF-center. The RF-length was obtained for that distance where neuronal response reached 50% (pink line).</p