Tyrosine hydroxylase (Th) expression has previously been reported in Purkinje cells (PCs) of rodents and humans, but its role in the regulation of behavior is not understood. Catecholamines are well known for facilitating cognitive behaviors and are expressed in many regions of the brain. Here, we investigated a possible role in cognitive behaviors of PC catecholamines, by mapping and testing functional roles of Th positive PCs in mice. Comprehensive mapping analyses revealed a distinct population of Th expressing PCs primarily in the posterior and lateral regions of the cerebellum (comprising about 18% of all PCs). To identify the role of PC catecholamines, we selectively knocked out Th in PCs using a conditional knockout approach, by crossing a Purkinje cell-selective Cre recombinase line, Pcp2-Cre, with a floxed tyrosine hydroxylase mouse line (Th^lox/lox) to produce Pcp2-Cre;Th^lox/lox mice. This manipulation resulted in approximately 50% reduction of Th protein expression in the cerebellar cortex and lateral cerebellar nucleus, but no reduction of Th in the locus coeruleus, which is known to innervate the cerebellum in mice. Pcp2-Cre;Th^lox/lox mice showed impairments in behavioral flexibility, response inhibition, social recognition memory, and associative fear learning relative to littermate controls, but no deficits in gross motor, sensory, instrumental learning, or sensorimotor gating functions. Catecholamines derived from specific populations of PCs appear to support cognitive functions, and their spatial distribution in the cerebellum suggests that they may underlie patterns of activation seen in human studies on the cerebellar role in cognitive function.

酪氨酸羟化酶（Th）的表达先前已在啮齿动物和人类的浦肯野细胞（PC）中被报道，但其在行为调节中的作用尚不清楚。儿茶酚胺因促进认知行为而闻名，并在大脑的许多区域表达。在这里，我们通过绘制和测试小鼠中 Th 阳性 PC 的功能作用，研究了 PC 儿茶酚胺在认知行为中的可能作用。全面的图谱分析揭示了表达 Th 的 PC 的独特群体主要位于小脑的后部和外侧区域（约占所有 PC 的 18%）。为了确定 PC 儿茶酚胺的作用，我们使用条件敲除方法，通过将浦肯野细胞选择性 Cre 重组酶系 Pcp2-Cre 与 floxed 酪氨酸羟化酶小鼠系 (Th ^lox/lox ) 杂交，选择性敲除 PC 中的 Th产生 Pcp2-Cre;Th ^lox/lox小鼠。这种操作导致小脑皮质和小脑外侧核中的 Th 蛋白表达减少约 50%，但蓝斑中的 Th 蛋白表达没有减少，而蓝斑是已知的支配小鼠小脑的区域。与同窝对照小鼠相比，Pcp2-Cre;Th ^lox/lox小鼠在行为灵活性、反应抑制、社会识别记忆和联想恐惧学习方面表现出损害，但在粗大运动、感觉、工具学习或感觉运动门控功能方面没有缺陷。源自特定 PC 群体的儿茶酚胺似乎支持认知功能，它们在小脑中的空间分布表明它们可能是人类关于小脑在认知功能中的作用的研究中发现的激活模式的基础。