, 2007). Consistent with this, inhibitory inputs mostly contact the dendritic shaft, and one observes sublinear summation when neighboring inhibitory inputs are integrated by pyramidal neurons, or when neighboring excitatory inputs are received by aspiny neurons ( Tamás et al., 2002). Spiny check details dendrites can also integrate inputs in a non-linear regime. Local dendritic spikes (also known

as “calcium spikes,” “calcium plateaus,” or “NMDA spikes”) are generated by focal stimulation of a dendrite (Holthoff et al., 2004, Polsky et al., 2009, Schiller et al., 2000 and Yuste et al., 1994). With two-photon uncaging, linear summation is observed when up to 30 neighboring spines are stimulated, although, if more inputs are stimulated, local spikes are triggered (Losonczy and Magee, 2006). A dendritic spike is a nonlinear phenomenon that bypasses the “synaptic democracy” and prevents the integration of additional inputs. But dendritic spikes could also significantly enrich the computational repertoire of the neuron, enabling the functional association of local inputs (Mel, 1994). Also, dendritic spikes, like the ones that occur in the distal apical dendrite Ulixertinib research buy of neocortical pyramidal neurons,

could enable the amplification of distant inputs that would otherwise not be transmitted to the soma (Larkum et al., 2009 and Yuste et al., 1994). Other functions of these local spikes could be to generate either intrinsic firing patterns (Elaagouby and Yuste, 1999) or persistent activity by the neuron (Major et al., 2008). Finally, local dendritic spikes can generate a strong form of LTD (Holthoff et al., 2004) that could be used as a “punishing signal” to prevent input association and, paradoxically, help preserve linear integration. But regardless of the presence or absence of local dendritic spikes, the neuron still has to solve the conductance shunting problem that arises with simultaneous activation of inputs. Given that, in vivo, dendrites are probably bombarded

with hundreds or perhaps even thousands of active inputs at any given time, if excitatory inputs were located on dendritic shafts, dendrites could be essentially Etomidate short-circuited all the time, making it impossible for voltage signals, including local dendritic spikes, to propagate along. The neuron would also be more reliable if its dendritic integration and signaling were constant under different conditions of synaptic inputs. For all of these reasons, it appears advantageous for the neuron to protect itself from the large conductance changes associated with synaptic transmission, and electrically isolating excitatory inputs into spines could be a solution to this problem. Spines could use neck filtering to ensure a nonsaturating regime of integration and fully exploit the benefits of a distributed input connectivity and, in addition, make dendritic integration more reliable and less dependent on the amount of synaptic activity present.