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Gao, P. P.

Publications and source records attributed to Gao, P. P..

2 recordsLinked to original sources

Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron

Dendritic spikes in thin dendritic branches (basal and oblique dendrites) of pyramidal neurons are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially-restricted glutamatergic inputs. Local dendritic potentials lasted 200-500 ms and propagated to the cell body where they caused sustained 10-20 mV depolarizations. Plateau potentials propagating from dendrite to soma, and action potentials propagating from soma to dendrite, created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and back-propagating action potentials, superimposed on each other. Our model replicated these experimental observations and made predictions, which were tested in experiments. Dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state ("prepared state"), characterized by depolarized membrane potential and faster membrane responses. The prepared state provides a time window of 200-500 ms during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles. New & NoteworthyIn cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials using voltage imaging, and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state -- a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

neuroscience↗

Layer-Specific Molecular Dynamics of PKMζ in Sensorimotor Cortex During Acquisition and Storage of Procedural Memory

Procedural memories, such as for riding a bicycle, can be maintained without practice for long periods of time and are thought to be supported by the persistent reorganization of sensorimotor cortices (S1/M1). Whereas enhanced synaptic strength and structural changes accompany the learning of motor tasks, the persistent molecular modifications that store long-term procedural memories within specific layers of sensorimotor cortex have not been identified. The persistent increase in the autonomously active, atypical PKC isoform, PKM{zeta}, is a putative molecular mechanism for maintaining enhanced synaptic strength during long-term potentiation (LTP) and several forms of long-term memory. Here we examine whether persistent increases in PKM{zeta} store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Perturbing PKM{zeta} synthesis with PKM{zeta} -antisense oligodeoxynucleotides or blocking atypical PKC activity with zeta inhibitory peptide (ZIP) in S1/M1 disrupts and erases the maintenance of long-term motor memories. Only memories that are maintained without daily reinforcement are affected, indicating atypical PKCs (via ZIP) and PKM{zeta} specifically (via antisense) stores consolidated long-term procedural memories. Analysis of changes in the amount of PKM{zeta} in S1/M1 reveals PKM{zeta} increases in layers II/III and V of both S1 and M1 cortices as performance improves to an asymptote during training. After storage for 1 month without reinforcement, the increase in M1 layer V but not other layers persists without decrement. Thus, the sustained increases in PKM{zeta} reveal that the persistent molecular changes storing long-term procedural memory are localized to the descending output layer of primary motor cortex.

neuroscience↗