Via Ca 2+ -imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, for each day the ensemble representation of this environment involved a unique subset of cells. Yet, cells within the ∼15-25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.CA1 place cells are considered crucial for spatial memory, but data is limited regarding whether their representations of space evolve over time scales of weeks or more 1 . Some theories suggest place cells should retain stable place fields for long-term retention of familiar environments 1 . Alternatively, dynamic aspects of place coding may facilitate distinct memory traces of different events occurring in the same environment 2 .Due to technical limitations, it has been only partially explored if CA1 representations of familiar environments are stable or evolve over time. Electrical recordings from many tens of cells are feasible 3 , but it is challenging to record from the same cells longer than a few days. Data on place fields' stability has largely been from small numbers of cells recorded over at most a week [4][5][6][7][8][9][10] . These studies have demonstrated cells with stable place fields, but the data have been too sparse to assess how coding evolves at the ensemble level.To study long-term coding dynamics, we combined (Fig. 1a): a viral vector (AAV2/5-CamKIIα-GCaMP3) to express the Ca 2+ -indicator GCaMP3 11 in pyramidal cells; a chronic mouse preparation for time-lapse imaging of CA1 over weeks 12 ; and a miniaturized (<2 g) microscope for Ca 2+ -imaging in hundreds of cells in freely behaving mice 13 . We thereby tracked somatic Ca 2+ dynamics of 515-1040 pyramidal cells in individual mice as they repeatedly visited a familiar track over 45 days.

Kinesin is a two-headed, ATP-driven motor protein that moves processively along microtubules in discrete steps of 8 nm, probably by advancing each of its heads alternately in sequence. Molecular details of how the chemical energy stored in ATP is coupled to mechanical displacement remain obscure. To shed light on this question, a force clamp was constructed, based on a feedback-driven optical trap capable of maintaining constant loads on single kinesin motors. The instrument provides unprecedented resolution of molecular motion and permits mechanochemical studies under controlled external loads. Analysis of records of kinesin motion under variable ATP concentrations and loads revealed several new features. First, kinesin stepping appears to be tightly coupled to ATP hydrolysis over a wide range of forces, with a single hydrolysis per 8-nm mechanical advance. Second, the kinesin stall force depends on the ATP concentration. Third, increased loads reduce the maximum velocity as expected, but also raise the apparent Michaelis-Menten constant. The kinesin cycle therefore contains at least one load-dependent transition affecting the rate at which ATP molecules bind and subsequently commit to hydrolysis. It is likely that at least one other load-dependent rate exists, affecting turnover number. Together, these findings will necessitate revisions to our understanding of how kinesin motors function.

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.