Biomedical subjects

Lindsey L Glickfeld

Publications and source records attributed to Lindsey L Glickfeld.

4 recordsLinked to original sources

PubMed2006

Distinct timing in the activity of cannabinoid-sensitive and cannabinoid-insensitive basket cells.

Cannabinoids are powerful modulators of inhibition, yet the precise spike timing of cannabinoid receptor (CB1R)-expressing inhibitory neurons in relation to other neurons in the circuit is poorly understood. Here we found that the spike timing of CB1R-expressing basket cells, a major target for cannabinoids in the rat hippocampus, was distinct from the other main group of basket cells, the CB1R-negative. Despite receiving the same afferent inputs, the synaptic and biophysical properties of the two cell types were tuned to detect different features of activity. CB1R-negative basket cells responded reliably and immediately to subtle and repetitive excitation. In contrast, CB1R-positive basket cells responded later and did not follow repetitive activity, but were better suited to integrate the consecutive excitation of independent afferents. This temporal separation in the activity of the two basket cell types generated distinct epochs of somatic inhibition that were differentially affected by endocannabinoids.

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PubMed2005

Self-administering cannabinoids.

Endocannabinoids, which are typically released by principal cells in response to prolonged depolarization, act as retrograde messengers to inhibit synaptic transmission. A recent study shows that in a specific subtype of cortical interneuron, endocannabinoids released under similar circumstances can also act cell-autonomously. Here, endocannabinoids endow these neurons with a memory of their own activity in the form of a long-term change in excitability.

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PubMed2004

Sensory neuron signaling to the brain: properties of transmitter release from olfactory nerve terminals.

Olfactory receptor neurons (ORNs) convey sensory information directly to the CNS via conventional glutamatergic synaptic contacts in olfactory bulb glomeruli. To better understand the process by which information contained in the odorant-evoked firing of ORNs is transmitted to the brain, we examined the properties of glutamate release from olfactory nerve (ON) terminals in slices of the rat olfactory bulb. We show that marked paired pulse depression is the same in simultaneously recorded periglomerular and tufted neurons, and that this form of short-term plasticity is attributable to a reduction of glutamate release from ON terminals. We used the progressive blockade of NMDA receptor (NMDAR) EPSCs by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-10-imine hydrogen maleate] and stationary fluctuation analysis of AMPA receptor (AMPAR) EPSCs to determine the probability of release (P(r)) of ON terminals; both approaches indicated that P(r) is unusually high (>/=0.8). The low-affinity glutamate receptor antagonists gamma-d-glutamylglycine and l-amino-5-phosphonovaleric acid blocked ON-evoked AMPAR- and NMDAR-mediated EPSCs, respectively, to the same extent under conditions of low and high P(r), suggesting that multivesicular release is not a feature of ON terminals. Although release from most synapses exhibits a highly nonlinear dependence on extracellular Ca(2+), we find that the relationship between glutamate release and extracellular Ca(2+) at ON terminals is nearly linear. Our results suggest that ON terminals have specialized features that may contribute to the reliable transmission of sensory information from nose to brain.

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PubMed2004

Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway.

At central synapses, P/Q-type Ca(2+) channels normally provide a critical Ca(2+) entry pathway for neurotransmission. Nevertheless, we found that nerve terminals lacking alpha(1A) (Ca(V)2.1), the pore-forming subunit of P/Q-type channels, displayed a remarkable preservation of synaptic function. Two consistent physiological changes reflective of synaptic homeostasis were observed in cultured hippocampal neurons derived from alpha(1A) (-/-) mice. First, the presynaptic response to an ionophore-mediated Ca(2+) elevation was 50% greater, indicating an enhanced Ca(2+) sensitivity of the release machinery. Second, basal miniature excitatory postsynaptic current frequency in alpha(1A) (-/-) neurons was increased 2-fold compared with WT neurons and occluded the normal response of presynaptic terminals to cAMP elevation, suggesting that the compensatory mechanism in alpha(1A) (-/-) synapses and the modulation of presynaptic function by PKA might share a final common pathway. We used cDNA microarray analysis to identify molecular changes underlying homeostatic regulation in the alpha(1A) (-/-) hippocampus. The 40,000 entries in our custom-made array included likely targets of presynaptic homeostasis, along with many other transcripts, allowing a wide-ranging examination of gene expression. The developmental pattern of changes in transcript levels relative to WT was striking; mRNAs at 5 and 11 days postnatal showed little deviation, but clear differences emerged by 22 days. Many of the transcripts that differed significantly in abundance corresponded to known genes that could be incorporated within a logical pattern consistent with the modulation of presynaptic function. Changes in endocytotic proteins, signal transduction kinases, and candidates for Ca(2+)-sensing molecules were consistent with implications of the direct physiological experiments.

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