Bcl-xL dependency coincides with the onset of neurogenesis in the developing mammalian spinal cord.

The bcl-2 family of survival and death promoting proteins play a key role in regulating cell numbers during nervous system development. Bcl-xL, an anti-apoptotic bcl-2 family member is highly expressed in the developing nervous system. However; the early embryonic lethality of the bcl-x germline null mouse precluded an investigation into its role in nervous system development. To identify the role of bcl-x in spinal cord neurogenesis, we generated a central nervous system-specific bcl-x conditional knockout (BKO) mouse. Apoptotic cell death in the BKO embryo was initially detected at embryonic day 11 (E11) in the ventrolateral aspect of the spinal cord corresponding to the location of motor neurons. Apoptosis reached its peak at E13 having spread across the ventral and into the dorsal spinal cord. By E18, the wave of apoptosis had passed and only a few apoptotic cells were observed. The duration and direction of spread of apoptosis across the spinal cord is consistent with the spatial and temporal sequence of neuronal differentiation. Motor neurons, the first neurons to become post mitotic in the spinal cord, were also the first apoptotic cells. As neurogenesis spread across the spinal cord, later born neuronal populations such as Lim2+ interneurons were also affected. The onset of apoptosis occurred in cells that had exited the cell cycle within the previous 24h and initiated neural differentiation as demonstrated by BrdU birthdating and ßIII tubulin immunohistochemistry. This data demonstrates that spinal cord neurons become Bcl-xL dependent at an early post mitotic stage in developmental neurogenesis.

In a daily time-place learning task, time is only used as a discriminative stimulus if each daily session is associated with a distinct spatial location.

It is difficult for rats to acquire daily time-place (TP) learning tasks. One theory suggests that rats do not use time of day as a stimulus signaling a specific response. In the present study, we tested rats' ability to use time of day as a discriminative stimulus. A fixed-interval procedure was used in which one lever provided reinforcement on a FI-5-s schedule in morning sessions, and the same lever provided reinforcement on a FI-30-s schedule in afternoon sessions. Because only one place was used in this paradigm, the rats could only use time of day to acquire the task. Mean responses during the first 5 s of the first trial in each session indicated that the rats did not discriminate between the two sessions. In Phase II, a different lever location was used for each of the two daily sessions, which meant that both spatial and temporal information could be used to acquire the task. The rats readily acquired the task in this phase, and probe trials indicated that the rats were using a combination of spatial and temporal information to discriminate between the two different trial types. When the spatial cue was removed in Phase III, rats no longer discriminated the two sessions, suggesting that time can only be used as a discriminative stimulus when each daily session is associated with a distinct spatial location.