Long‐Term Fine Motor Capability on the Staircase Test Correlates with the Absolute Number, but Not the Density, of DARPP‐Positive Neurons in the Caudate‐Putamen

Abstract

Measurement of long-term functional and anatomical outcomes in the same animal is considered a powerful strategy for correlating structure with function. In a neonatal animal model of hypoxic-ischemic brain injury that is relevant to cerebral palsy, long-term functional deficits on the staircase test and long-term anatomical deficits in the absolute number of medium-spiny projection neurons in the caudate-putamen were reported in different animals due to logistical constraints. Here, we investigated if these functional and anatomical measures were correlated when measured in the same animals. The medium-spiny projection neurons were investigated because (1) they comprise the vast majority (>97%) of all neurons in the caudate-putamen and (2) motor deficits observed during staircase testing are likely to involve these striatal medium-spiny projection neurons through their connections. We found that long-term skilled forepaw capability on the staircase test was correlated with the absolute number of DARPP-32-positive medium-spiny projection neurons in the caudate-putamen. Specifically, deficits in skilled forepaw ability for the number of sugar pellets eaten and retrieved, and for the maximum staircase level reached, were significantly correlated with a lower absolute neuronal number. We also found that skilled forepaw ability on the staircase test was not correlated with the neuronal density (i.e., number per unit volume) of DARPP-32-positive medium-spiny projection neurons. Since neuronal density is an indirect measure of neuronal survival that is used in the literature, and absolute neuronal number is a direct measure, the results also highlight the scientific value of measuring absolute neuronal number.

Four-dimensional mapping of dynamic longitudinal brain subcortical development and early learning functions in infants

“…58, the authors also confirmed the association between the reduced volume of the caudate nuclei and the impaired fine movement coordination in patients with hippocampal atrophy aged from 9 to 25 years of age. In addition, a neonatal animal study 59 demonstrated that the number of the medium-spiny projection neurons, the principal neurons which account for around 95% of all the neurons in the striatum, is significantly associated with the long-term fine motor capability on the staircase test. Taken together, the striatum should undertake key elements in the establishment of fine motor.…”