Intrinsic signal optical imaging with red illumination (ISOI) is used extensively to provide high spatial resolution maps of stimulusevoked hemodynamic-related signals as an indirect means to map evoked neuronal activity. This evoked signal is generally described as beginning with an undershoot or "dip" in signal that is faster, more transient, and weaker compared with the subsequent signal overshoot. In contrast, the evoked signal detected with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is generally described as containing an undershoot after the initial dip and overshoot, even though it, too, detects hemodynamic-related signals and its first two phases appear complementary to those of ISOI. Here, we used ISOI with 635 nm illumination to image over 13.5 s after a 1 s stimulus delivery to detect and successfully use the ISOI undershoot phase for functional mapping. Eight spatiotemporal attributes were assessed per signal phase including maximum areal extent and peak magnitude, both of which were largest for the ISOI overshoot, followed by the undershoot and then the initial dip. Peak activity location did not colocalize well between the three phases; furthermore, we found mostly modest correlations between attributes within each phase and sparse correlations between phases. Extended (13.5 s) electrophysiology recordings did not exhibit a reoccurrence of evoked suprathreshold or subthreshold neuronal responses that could be associated with the undershoot. Beyond the undershoot, additional overshoot/undershoot fluctuations were also mapped, but were typically less spatiotemporally specific to stimulus delivery. Implications for ISOI and BOLD fMRI are discussed.

Intrinsic Signal Optical Imaging (ISOI) can be used to map cortical function and organization. Because its detected signal lasts 10+ sec consisting of three phases, trials are typically collected using a long (tens of seconds) stimulus delivery interval (SDI) at the expense of efficiency, even when interested in mapping only the first signal phase (e.g., ISOI initial dip). It is unclear how the activity profile can change when stimuli are delivered at shorter intervals, and whether a short SDI can be implemented to improve efficiency. The goals of the present study are two-fold: characterize the ISOI activity profile when multiple stimuli are delivered at 4 sec intervals, and determine whether successful mapping can be attained from trials collected using an SDI of 4 sec (offering >10× increase in efficiency). Our results indicate that four stimuli delivered 4 sec apart evoke an activity profile different from the triphasic signal, consisting of signal dips in a series at the same frequency as the stimuli despite a strong rise in signal prior to the 2 nd -4 th stimuli. Visualization of such signal dips is dependent on using a baseline immediately prior to every stimulus. Use of the 4-sec SDI is confirmed to successfully map activity with a similar location in peak activity and increased areal extent and peak magnitude compared to using a long SDI. Additional experiments were performed to begin addressing issues such as SDI temporal jittering, response magnitude as a function of SDI duration, and application for successful mapping of cortical function topography.

We have previously demonstrated that exposure of adult rat to a type of enriched environment, known as ‘naturalistic habitat’ (NH), induces extensive functional plasticity in the whiskers’ representations within the primary somatosensory cortex. Here we have investigated the molecular basis for such functional plasticity involved in this model. Based on the role of BDNF on synaptic plasticity and neuronal growth, the focus of this study is on BDNF and its downstream effectors CREB, synapsin I, and GAP-43. In particular, we determined the effects of natural whiskers use during 2, 7 or 28 days exposure to a NH on barrel cortex and hippocampus, as compared to standard cage controls. Naturalistic whiskers use resulted in increased levels of mRNAs and proteins for BDNF and its downstream effectors. Level changes for these markers were already detected after 2 days in the naturalistic habitat and grew larger over longer exposures (7 and 28 days). The cerebral cortex was found to be sensitive to the naturalistic habitat exposure at all time points, and more sensitive than the hippocampus to the trimming of the whiskers. Trimming of the whiskers decreased the level of most of the markers under study suggesting that whiskers exert a tonic influence on plasticity markers that can be further enhanced by naturalistic use. These results implicate BDNF and its downstream effectors in the plasticity induced by the naturalistic habitat. The critical action of experience on molecular substrates of plasticity seems to provide molecular basis for the design of experienced-based rehabilitative strategies to enhance brain function.